Patent Publication Number: US-2023151366-A1

Title: COMPOSITIONS AND METHODS OF INHIBITING SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-CoV-2)

Description:
SEQUENCE LISTING 
     The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled BIOL0391WOSEQ_ST25.txt created Apr. 12, 2021, which is 194 kb in size. The information in the electronic format of the sequence listing is incorporated herein by reference in its entirety. 
     FIELD 
     Embodiments described herein relate to compounds, compositions, and methods for inhibiting the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and preventing or treating its associated disease, Coronavirus Disease 2019 (COVID-19). 
     BACKGROUND 
     The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) is a global pandemic that has infected over 2 million people and killed over 139,000 people worldwide as of Apr. 16, 2020 according to the Johns Hopkins Coronavirus Resource Center Dashboard. These numbers represent the total confirmed cases, but the true numbers of infections and deaths are surely higher due to underreporting and the shortage of testing. The true number of infections has been estimated up to 10 times higher. 
     SARS-CoV-2 is highly contagious. It has a long incubation period of 1 to 14 days of contagiousness before an infected individual shows symptoms, if at all. A recent report indicated that COVID-19 may be most contagious 1 to 2 days before symptoms appear. Infected but asymptomatic individuals are dubbed superspreaders. The infection is spreading exponentially and the doubling time of the number of infected persons was estimated at approximately 2 days in the United States in March 2020 but has recently been estimated at 6.5 days on Apr. 7, 2020. 
     The most common symptoms of COVID-19 are fever, fatigue, and dry cough. For some individuals, especially the elderly and people with underlying medical conditions, COVID-19 can cause difficulty breathing leading to hospitalization and intubation with a ventilator because patients can no longer breathe on their own. COVID-19 is fatal when patients succumb to lung damage, respiratory failure, and/or pneumonia. 
     In addition to the public health crisis caused by SARS-CoV-2 and COVID-19, the pandemic has also caused severe economic duress. In the United States, where states have mandated sheltering at home and social distancing to flatten the curve of infection, 22 million people have become unemployed ever since a national energy over COVID-19 was declared on Mar. 13, 2020. 
     Currently, no vaccine or approved therapy for SARS-CoV-2 and COVID-19 exists. Although social distancing and sheltering at home appears to be dampening the forecast on the number of COVID-19 deaths in the United States from the 100,000-240,000 range to approximately 60,000 according to a model from the University of Washington, there is an urgent need for a therapeutic against SARS-CoV-2 to stop the pandemic. 
     SUMMARY 
     Embodiments described herein relate to the design and synthesis of compounds and compositions that can be administered to inhibit the replication or infectivity of SARS-CoV-2 and to prevent or treat (COVID-19). 
    
    
     DETAILED DESCRIPTION 
     It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the embodiments, as claimed. Herein, the use of the singular includes the plural unless specifically stated otherwise. As used herein, the use of “or” means “and/or” unless stated otherwise. Furthermore, the use of the term “including” as well as other forms, such as “includes” and “included”, is not limiting. 
     The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents, or portions of documents, cited in this application, including, but not limited to, patents, patent applications, articles, books, treatises, and GenBank and NCBI reference sequence records are hereby expressly incorporated by reference for the portions of the document discussed herein, as well as in their entirety. 
     It is understood that the sequence set forth in each SEQ ID NO in the examples contained herein is independent of any modification to a sugar moiety, an internucleoside linkage, or a nucleobase. As such, compounds defined by a SEQ ID NO may comprise, independently, one or more modifications to a sugar moiety, an internucleoside linkage, or a nucleobase. Compounds described by ION number indicate a combination of nucleobase sequence, chemical modification, and motif. 
     Unless otherwise indicated, the following terms have the following meanings: 
     “2′-deoxynucleoside” means a nucleoside comprising 2′-H(H) furanosyl sugar moiety, as found in naturally occurring deoxyribonucleic acids (DNA). In certain embodiments, a 2′-deoxynucleoside may comprise a modified nucleobase or may comprise an RNA nucleobase (uracil). 
     “2′-O-methoxyethyl” (also 2′-MOE, MOE, methoxyethyl, and 2′-O(CH 2 ) 2 —OCH 3 ) refers to an O-methoxy-ethyl modification at the 2′ position of a furanosyl ring. A 2′-O-methoxyethyl modified sugar is a modified sugar. 
     “2′-MOE nucleoside” (also 2′-O-methoxyethyl nucleoside) means a nucleoside comprising a 2′-MOE modified sugar moiety. 
     “2′-substituted nucleoside” or “2-modified nucleoside” means a nucleoside comprising a 2′-substituted or 2′-modified sugar moiety. As used herein, “2′-substituted” or “2-modified” in reference to a sugar moiety means a sugar moiety comprising at least one 2′-substituent group other than H or OH. 
     “3′ target site” refers to the nucleotide of a target nucleic acid which is complementary to the 3′-most nucleotide of a particular compound. 
     “5′ target site” refers to the nucleotide of a target nucleic acid which is complementary to the 5′-most nucleotide of a particular compound. 
     “5-methylcytosine” means a cytosine with a methyl group attached to the 5 position. 
     “About” means within ±10% of a value. For example, if it is stated, “the compounds affected about 70% inhibition of SARS-CoV-2”, it is implied that SARS-CoV-2 levels are inhibited within a range of 60% and 80%. 
     “Administration” or “administering” refers to routes of introducing a compound or composition provided herein to an individual to perform its intended function. An example of a route of administration that can be used includes, but is not limited to inhalation such as through a nebulizer or inhaler. 
     “Administered concomitantly” or “co-administration” means administration of two or more compounds in any manner in which the pharmacological effects of both are manifest in the patient. Concomitant administration does not require that both compounds be administered in a single pharmaceutical composition, in the same dosage form, by the same route of administration, or at the same time. The effects of both compounds need not manifest themselves at the same time. The effects need only be overlapping for a period of time and need not be coextensive. Concomitant administration or co-administration encompasses administration in parallel or sequentially. 
     “Amelioration” refers to an improvement or lessening of at least one indicator, sign, or symptom of an associated disease, disorder, or condition. In certain embodiments, amelioration includes a delay or slowing in the progression or severity of one or more indicators of a condition or disease. The progression or severity of indicators may be determined by subjective or objective measures, which are known to those skilled in the art. 
     “Animal” refers to a human or non-human animal, including, but not limited to, mice, rats, rabbits, dogs, cats, pigs, and non-human primates, including, but not limited to, monkeys and chimpanzees. 
     “Antisense activity” means any detectable and/or measurable activity attributable to the hybridization of an antisense compound to its target nucleic acid. In certain embodiments, antisense activity is a decrease in the amount or expression of a target nucleic acid or protein encoded by such target nucleic acid compared to target nucleic acid levels or target protein levels in the absence of the antisense compound to the target. 
     “Antisense compound” means a compound comprising an oligonucleotide and optionally one or more additional features, such as a conjugate group or terminal group. Examples of antisense compounds include single-stranded and double-stranded compounds, such as, oligonucleotides, ribozymes, siRNAs, shRNAs, ssRNAs, and occupancy-based compounds. 
     “Antisense inhibition” means reduction of target nucleic acid levels in the presence of an antisense compound complementary to a target nucleic acid compared to target nucleic acid levels in the absence of the antisense compound. 
     “Antisense mechanisms” are all those mechanisms involving hybridization of a compound with target nucleic acid, wherein the outcome or effect of the hybridization is either target degradation or target occupancy with concomitant stalling of the cellular machinery involving, for example, transcription or splicing. 
     “Antisense oligonucleotide” means an oligonucleotide having a nucleobase sequence that is complementary to a target nucleic acid or region or segment thereof. In certain embodiments, an antisense oligonucleotide is specifically hybridizable to a target nucleic acid or region or segment thereof. 
     “Bicyclic nucleoside” or “BNA” means a nucleoside comprising a bicyclic sugar moiety. “Bicyclic sugar” or “bicyclic sugar moiety” means a modified sugar moiety comprising two rings, wherein the second ring is formed via a bridge connecting two of the atoms in the first ring thereby forming a bicyclic structure. In certain embodiments, the first ring of the bicyclic sugar moiety is a furanosyl moiety. In certain embodiments, the bicyclic sugar moiety does not comprise a furanosyl moiety. 
     “Branching group” means a group of atoms having at least 3 positions that are capable of forming covalent linkages to at least 3 groups. In certain embodiments, a branching group provides a plurality of reactive sites for connecting tethered ligands to an oligonucleotide via a conjugate linker and/or a cleavable moiety. 
     “Cell-targeting moiety” means a conjugate group or portion of a conjugate group that is capable of binding to a particular cell type or particular cell types. 
     “cEt” or “constrained ethyl” means a bicyclic furanosyl sugar moiety comprising a bridge connecting the 4′-carbon and the 2′-carbon, wherein the bridge has the formula: 4′-CH(CH 3 )—O-2′. 
     “cEt nucleoside” means a nucleoside comprising a cEt modified sugar moiety. 
     “Chemical modification” in a compound describes the substitutions or changes through chemical reaction, of any of the units in the compound relative to the original state of such unit. “Modified nucleoside” means a nucleoside having, independently, a modified sugar moiety and/or modified nucleobase. “Modified oligonucleotide” means an oligonucleotide comprising at least one modified internucleoside linkage, a modified sugar, and/or a modified nucleobase. 
     “Chemically distinct region” refers to a region of a compound that is in some way chemically different than another region of the same compound. For example, a region having 2′-O-methoxyethyl nucleotides is chemically distinct from a region having nucleotides without 2′-O-methoxyethyl modifications. 
     “Chimeric antisense compounds” means antisense compounds that have at least 2 chemically distinct regions, each position having a plurality of subunits. 
     “Chirally enriched population” means a plurality of molecules of identical molecular formula, wherein the number or percentage of molecules within the population that contain a particular stereochemical configuration at a particular chiral center is greater than the number or percentage of molecules expected to contain the same particular stereochemical configuration at the same particular chiral center within the population if the particular chiral center were stereorandom. Chirally enriched populations of molecules having multiple chiral centers within each molecule may contain one or more stereorandom chiral centers. In certain embodiments, the molecules are modified oligonucleotides. In certain embodiments, the molecules are compounds comprising modified oligonucleotides. 
     “Cleavable bond” means any chemical bond capable of being split. In certain embodiments, a cleavable bond is selected from among: an amide, a polyamide, an ester, an ether, one or both esters of a phosphodiester, a phosphate ester, a carbamate, a di-sulfide, or a peptide. 
     “Cleavable moiety” means a bond or group of atoms that is cleaved under physiological conditions, for example, inside a cell, an animal, or a human. 
     “Complementary” in reference to an oligonucleotide means the nucleobase sequence of such oligonucleotide or one or more regions thereof matches the nucleobase sequence of another oligonucleotide or nucleic acid or one or more regions thereof when the two nucleobase sequences are aligned in opposing directions. Nucleobase matches or complementary nucleobases, as described herein, are limited to the following pairs: adenine (A) and thymine (T), adenine (A) and uracil (U), cytosine (C) and guanine (G), and 5-methyl cytosine ( m C) and guanine (G) unless otherwise specified. Complementary oligonucleotides and/or nucleic acids need not have nucleobase complementarity at each nucleoside and may include one or more nucleobase mismatches. By contrast, “fully complementary” or “100% complementary” in reference to oligonucleotides means that such oligonucleotides have nucleobase matches at each nucleoside without any nucleobase mismatches. 
     “Conjugate group” means a group of atoms that is attached to an oligonucleotide. Conjugate groups include a conjugate moiety and a conjugate linker that attaches the conjugate moiety to the oligonucleotide. 
     “Conjugate linker” means a group of atoms comprising at least one bond that connects a conjugate moiety to an oligonucleotide. 
     “Conjugate moiety” means a group of atoms that is attached to an oligonucleotide via a conjugate linker. 
     “Contiguous” in the context of an oligonucleotide refers to nucleosides, nucleobases, sugar moieties, or internucleoside linkages that are immediately adjacent to each other. For example, “contiguous nucleobases” means nucleobases that are immediately adjacent to each other in a sequence. 
     “Coronavirus Disease 2019 (COVID-19)” refers to the disease caused by the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and includes, but is not limited to, one or more symptoms associated with SARS-CoV-2 infection such as respiratory illness, difficulty breathing, fever, cough, fatigue, aches and pains, sore throat, runny nose, diarrhea, loss of taste or smell, and nasal congestion. 
     “Designing” or “Designed to” refer to the process of designing a compound that specifically hybridizes with a selected nucleic acid molecule. 
     “Diluent” means an ingredient in a composition that lacks pharmacological activity, but is pharmaceutically necessary or desirable. For example, the diluent in an injected composition can be a liquid, e.g. saline solution. 
     “Differently modified” means chemical modifications or chemical substituents that are different from one another, including absence of modifications. Thus, for example, a MOE nucleoside and an unmodified DNA nucleoside are “differently modified,” even though the DNA nucleoside is unmodified. Likewise, DNA and RNA are “differently modified,” even though both are naturally-occurring unmodified nucleosides. Nucleosides that are the same but for comprising different nucleobases are not differently modified. For example, a nucleoside comprising a 2′-OMe modified sugar and an unmodified adenine nucleobase and a nucleoside comprising a 2′-OMe modified sugar and an unmodified thymine nucleobase are not differently modified. 
     “Dose” means a specified quantity of a compound or pharmaceutical agent provided in a single administration, or in a specified time period. In certain embodiments, a dose may be administered in two or more boluses, tablets, or injections. For example, in certain embodiments, where subcutaneous administration is desired, the desired dose may require a volume not easily accommodated by a single injection. In such embodiments, two or more injections may be used to achieve the desired dose. In certain embodiments, a dose may be administered in two or more injections to minimize injection site reaction in an individual. In other embodiments, the compound or pharmaceutical agent is administered by infusion over an extended period of time or continuously. Doses may be stated as the amount of pharmaceutical agent per hour, day, week or month. 
     “Dosing regimen” is a combination of doses designed to achieve one or more desired effects. 
     “Double-stranded antisense compound” means an antisense compound comprising two oligomeric compounds that are complementary to each other and form a duplex, and wherein one of the two said oligomeric compounds comprises an oligonucleotide. 
     “Effective amount” means the amount of compound sufficient to effectuate a desired physiological outcome in an individual in need of the compound. The effective amount may vary among individuals depending on the health and physical condition of the individual to be treated, the taxonomic group of the individuals to be treated, the formulation of the composition, assessment of the individual&#39;s medical condition, and other relevant factors. 
     “Efficacy” means the ability to produce a desired effect. 
     “Expression” includes all the functions by which a gene&#39;s coded information is converted into structures present and operating in a cell. Such structures include, but are not limited to, the products of transcription and translation. 
     “Gapmer” means an oligonucleotide comprising an internal region having a plurality of nucleosides that support RNase H cleavage positioned between external regions having one or more nucleosides, wherein the nucleosides comprising the internal region are chemically distinct from the nucleoside or nucleosides comprising the external regions. The internal region may be referred to as the “gap” and the external regions may be referred to as the “wings.” 
     “Hybridization” means the annealing of oligonucleotides and/or nucleic acids. While not limited to a particular mechanism, the most common mechanism of hybridization involves hydrogen bonding, which may be Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleobases. In certain embodiments, complementary nucleic acid molecules include, but are not limited to, an antisense compound and a nucleic acid target. In certain embodiments, complementary nucleic acid molecules include, but are not limited to, an oligonucleotide and a nucleic acid target. 
     “Immediately adjacent” means there are no intervening elements between the immediately adjacent elements of the same kind (e.g. no intervening nucleobases between the immediately adjacent nucleobases). 
     “Individual” means a human or non-human animal selected for treatment or therapy. 
     “Inhibiting the expression or activity” refers to a reduction or blockade of the expression or activity relative to the expression of activity in an untreated or control sample and does not necessarily indicate a total elimination of expression or activity. 
     “Internucleoside linkage” means a group or bond that forms a covalent linkage between adjacent nucleosides in an oligonucleotide. “Modified internucleoside linkage” means any internucleoside linkage other than a naturally occurring, phosphate internucleoside linkage. Non-phosphate linkages are referred to herein as modified internucleoside linkages. 
     “Lengthened oligonucleotides” are those that have one or more additional nucleosides relative to an oligonucleotide disclosed herein, e.g. a parent oligonucleotide. 
     “Linked nucleosides” means adjacent nucleosides linked together by an internucleoside linkage. 
     “Linker-nucleoside” means a nucleoside that links an oligonucleotide to a conjugate moiety. Linker-nucleosides are located within the conjugate linker of a compound. Linker-nucleosides are not considered part of the oligonucleotide portion of a compound even if they are contiguous with the oligonucleotide. 
     “Mismatch” or “non-complementary” means a nucleobase of a first oligonucleotide that is not complementary to the corresponding nucleobase of a second oligonucleotide or target nucleic acid when the first and second oligonucleotides are aligned. For example, nucleobases including but not limited to a universal nucleobase, inosine, and hypoxanthine, are capable of hybridizing with at least one nucleobase but are still mismatched or non-complementary with respect to nucleobase to which it hybridized. As another example, a nucleobase of a first oligonucleotide that is not capable of hybridizing to the corresponding nucleobase of a second oligonucleotide or target nucleic acid when the first and second oligonucleotides are aligned is a mismatch or non-complementary nucleobase. 
     “Monomer” refers to a single unit of an oligomer. Monomers include, but are not limited to, nucleosides and nucleotides. 
     “Motif” means the pattern of unmodified and/or modified sugar moieties, nucleobases, and/or internucleoside linkages, in an oligonucleotide. 
     “Natural” or “naturally occurring” means found in nature. 
     “Non-bicyclic modified sugar” or “non-bicyclic modified sugar moiety” means a modified sugar moiety that comprises a modification, such as a substituent, that does not form a bridge between two atoms of the sugar to form a second ring. 
     “Nucleic acid” refers to molecules composed of monomeric nucleotides. A nucleic acid includes, but is not limited to, ribonucleic acids (RNA), deoxyribonucleic acids (DNA), single-stranded nucleic acids, and double-stranded nucleic acids. 
     “Nucleobase” means a heterocyclic moiety capable of pairing with a base of another nucleic acid. As used herein a “naturally occurring nucleobase” is adenine (A), thymine (T), cytosine (C), uracil (U), and guanine (G). A “modified nucleobase” is a naturally occurring nucleobase that is chemically modified. A “universal base” or “universal nucleobase” is a nucleobase other than a naturally occurring nucleobase and modified nucleobase, and is capable of pairing with any nucleobase. 
     “Nucleobase sequence” means the order of contiguous nucleobases in a nucleic acid or oligonucleotide independent of any sugar or internucleoside linkage. 
     “Nucleoside” means a compound comprising a nucleobase and a sugar moiety. The nucleobase and sugar moiety are each, independently, unmodified or modified. “Modified nucleoside” means a nucleoside comprising a modified nucleobase and/or a modified sugar moiety. Modified nucleosides include abasic nucleosides, which lack a nucleobase. 
     “Oligomeric compound” means a compound comprising a single oligonucleotide and optionally one or more additional features, such as a conjugate group or terminal group. 
     “Oligonucleotide” means a polymer of linked nucleosides each of which can be modified or unmodified, independent one from another. Unless otherwise indicated, oligonucleotides consist of 8-80 linked nucleosides. “Modified oligonucleotide” means an oligonucleotide, wherein at least one sugar, nucleobase, or internucleoside linkage is modified. “Unmodified oligonucleotide” means an oligonucleotide that does not comprise any sugar, nucleobase, or internucleoside modification. 
     “Parent oligonucleotide” means an oligonucleotide whose sequence is used as the basis of design for more oligonucleotides of similar sequence but with different lengths, motifs, and/or chemistries. The newly designed oligonucleotides may have the same or overlapping sequence as the parent oligonucleotide. 
     “Parenteral administration” means administration through injection or infusion. Parenteral administration includes subcutaneous administration, intravenous administration, intramuscular administration, intraarterial administration, intraperitoneal administration, or intracranial administration, e.g. intrathecal or intracerebroventricular administration. 
     “Pharmaceutically acceptable carrier or diluent” means any substance suitable for use in administering to an individual. For example, a pharmaceutically acceptable carrier can be a sterile aqueous solution, such as PBS or water-for-injection. 
     “Pharmaceutically acceptable salts” means physiologically and pharmaceutically acceptable salts of compounds, such as oligomeric compounds or oligonucleotides, i.e., salts that retain the desired biological activity of the parent compound and do not impart undesired toxicological effects thereto. 
     “Pharmaceutical agent” means a compound that provides a therapeutic benefit when administered to an individual. 
     “Pharmaceutical composition” means a mixture of substances suitable for administering to an individual. For example, a pharmaceutical composition may comprise one or more compounds or salt thereof and a sterile aqueous solution. 
     “Phosphorothioate linkage” means a modified phosphate linkage in which one of the non-bridging oxygen atoms is replaced with a sulfur atom. A phosphorothioate internucleoside linkage is a modified internucleoside linkage. 
     “Phosphorus moiety” means a group of atoms comprising a phosphorus atom. In certain embodiments, a phosphorus moiety comprises a mono-, di-, or tri-phosphate, or phosphorothioate. 
     “Portion” means a defined number of contiguous (i.e., linked) nucleobases of a nucleic acid. In certain embodiments, a portion is a defined number of contiguous nucleobases of a target nucleic acid. In certain embodiments, a portion is a defined number of contiguous nucleobases of an oligomeric compound. 
     “Prevent” refers to delaying or forestalling the onset, development or progression of a disease, disorder, or condition for a period of time from minutes to indefinitely. In the context of preventing COVID-19, “prevent” refers to forestalling the onset, development or progression of any symptoms associated with SARS-CoV-2 infection and/or delaying or forestalling the onset or increase in SARS-CoV-2 replication, infectivity, viral titer, or viral load in the individual. 
     “Prodrug” means a compound in a form outside the body which, when administered to an individual, is metabolized to another form within the body or cells thereof. In certain embodiments, the metabolized form is the active, or more active, form of the compound (e.g., drug). Typically conversion of a prodrug within the body is facilitated by the action of an enzyme(s) (e.g., endogenous or viral enzyme) or chemical(s) present in cells or tissues, and/or by physiologic conditions. 
     “Reduce” means to bring down to a smaller extent, size, amount, or number. 
     “RefSeq No.” is a unique combination of letters and numbers assigned to a sequence to indicate the sequence is for a particular target transcript (e.g., target gene). Such sequence and information about the target gene (collectively, the gene record) can be found in a genetic sequence database. Genetic sequence databases include the NCBI Reference Sequence database, GenBank, the European Nucleotide Archive, and the DNA Data Bank of Japan (the latter three forming the International Nucleotide Sequence Database Collaboration or INSDC). 
     “Region” is defined as a portion of the target nucleic acid having at least one identifiable structure, function, or characteristic. 
     “RNAi compound” means an antisense compound that acts, at least in part, through RISC or Ago2, but not through RNase H, to modulate a target nucleic acid and/or protein encoded by a target nucleic acid. RNAi compounds include, but are not limited to double-stranded siRNA, single-stranded RNA (ssRNA), and microRNA, including microRNA mimics. 
     “Segments” are defined as smaller or sub-portions of regions within a nucleic acid. 
     “Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2)” refers to all strains and isolates of coronavirus that causes COVID-19. 
     “SARS-CoV-2 specific inhibitor” refers to any agent capable of specifically inhibiting SARS-CoV-2 RNA and/or SARS-CoV-2 protein expression or activity at the molecular level. For example, SARS-CoV-2 specific inhibitors include nucleic acids (including antisense compounds), peptides, antibodies, small molecules, and other agents capable of inhibiting the expression of SARS-CoV-2 RNA and/or SARS-CoV-2 protein. 
     “Side effects” means physiological disease and/or conditions attributable to a treatment other than the desired effects. In certain embodiments, side effects include injection site reactions, liver function test abnormalities, renal function abnormalities, liver toxicity, renal toxicity, central nervous system abnormalities, myopathies, and malaise. For example, increased aminotransferase levels in serum may indicate liver toxicity or liver function abnormality. For example, increased bilirubin may indicate liver toxicity or liver function abnormality. 
     “Single-stranded” in reference to a compound means the compound has only one oligonucleotide. “Self-complementary” means an oligonucleotide that at least partially hybridizes to itself. A compound consisting of one oligonucleotide, wherein the oligonucleotide of the compound is self-complementary, is a single-stranded compound. A single-stranded compound may be capable of binding to a complementary compound to form a duplex. 
     “Sites” are defined as unique nucleobase positions within a target nucleic acid. 
     “Specifically hybridizable” refers to an oligonucleotide having a sufficient degree of complementarity between the oligonucleotide and a target nucleic acid to induce a desired effect, while exhibiting minimal or no effects on non-target nucleic acids. In certain embodiments, specific hybridization occurs under physiological conditions. 
     “Specifically inhibit” with reference to a target nucleic acid means to reduce or block expression of the target nucleic acid while exhibiting fewer, minimal, or no effects on non-target nucleic acids. Reduction does not necessarily indicate a total elimination of the target nucleic acid&#39;s expression. 
     “Stereorandom chiral center” in the context of a population of molecules of identical molecular formula means a chiral center having a random stereochemical configuration. For example, in a population of molecules comprising a stereorandom chiral center, the number of molecules having the (S) configuration of the stereorandom chiral center may be but is not necessarily the same as the number of molecules having the (R) configuration of the stereorandom chiral center. The stereochemical configuration of a chiral center is considered random when it is the result of a synthetic method that is not designed to control the stereochemical configuration. In certain embodiments, a stereorandom chiral center is a stereorandom phosphorothioate internucleoside linkage. 
     “Sugar moiety” means an unmodified sugar moiety or a modified sugar moiety. “Unmodified sugar moiety” or “unmodified sugar” means a 2′-OH(H) furanosyl moiety, as found in RNA (an “unmodified RNA sugar moiety”), or a 2′-H(H) moiety, as found in DNA (an “unmodified DNA sugar moiety”). Unmodified sugar moieties have one hydrogen at each of the 1′, 3′, and 4′ positions, an oxygen at the 3′ position, and two hydrogens at the 5′ position. “Modified sugar moiety” or “modified sugar” means a modified furanosyl sugar moiety or a sugar surrogate. “Modified furanosyl sugar moiety” means a furanosyl sugar comprising a non-hydrogen substituent in place of at least one hydrogen of an unmodified sugar moiety. In certain embodiments, a modified furanosyl sugar moiety is a 2′-substituted sugar moiety. Such modified furanosyl sugar moieties include bicyclic sugars and non-bicyclic sugars. 
     “Sugar surrogate” means a modified sugar moiety having other than a furanosyl moiety that can link a nucleobase to another group, such as an internucleoside linkage, conjugate group, or terminal group in an oligonucleotide. Modified nucleosides comprising sugar surrogates can be incorporated into one or more positions within an oligonucleotide and such oligonucleotides are capable of hybridizing to complementary compounds or nucleic acids. 
     “Targeting” means the specific hybridization of a compound to a target nucleic acid in order to induce a desired effect. 
     “Target nucleic acid,” “target RNA,” “target RNA transcript” and “nucleic acid target” all mean a nucleic acid capable of being targeted by compounds described herein. 
     “Target region” means a portion of a target nucleic acid to which one or more compounds is targeted. 
     “Target segment” means the sequence of nucleotides of a target nucleic acid to which a compound is targeted. “5′ target site” refers to the 5′-most nucleotide of a target segment. “3′ target site” refers to the 3′-most nucleotide of a target segment. 
     “Terminal group” means a chemical group or group of atoms that is covalently linked to a terminus of an oligonucleotide. 
     “Therapeutically effective amount” means an amount of a compound, pharmaceutical agent, or composition that provides a therapeutic benefit to an individual. 
     “Treat” refers to administering a compound or pharmaceutical composition to an individual in order to effect an alteration or improvement of a disease, disorder, or condition in the individual. In the context of treating COVID-19, “treat” refers to improving any symptoms associated with SARS-CoV-2 infection and/or inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load in the individual. 
     Certain Embodiments 
     Certain embodiments provide methods, compounds and compositions for inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load, thereby inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load in the lung cells. 
     Certain embodiments provide compounds targeted to SARS-CoV-2 RNA. In certain embodiments, the SARS-CoV-2 RNA has the sequence set forth in GENBANK Accession No. NC_045512.2, which is incorporated by reference in its entirety and designated herein as SEQ ID NO: 1. In certain embodiments, the SARS-CoV-2 RNA has the sequence set forth in the complement of GENBANK Accession No. NC_045512.2, designated herein as SEQ ID NO: 2, which is the complement of genomic sequence of severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, designated herein as SEQ ID NO: 2 (the complement of GENBANK Accession No. NC_045512.2). 
     In certain embodiments, the compound is an antisense compound or oligomeric compound. In certain embodiments, the compound is single-stranded. In certain embodiments, the compound is double-stranded. 
     Certain embodiments provide a compound comprising a modified oligonucleotide consisting of 8 to 80 linked nucleosides and having a nucleobase sequence comprising at least 8 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. In certain embodiments, the compound is an antisense compound or oligomeric compound. In certain embodiments, the compound is single-stranded. In certain embodiments, the compound is double-stranded. In certain embodiments, the modified oligonucleotide consists of 10 to 30 linked nucleosides. 
     Certain embodiments provide a compound comprising a modified oligonucleotide consisting of 9 to 80 linked nucleosides and having a nucleobase sequence comprising at least 9 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. In certain embodiments, the compound is an antisense compound or oligomeric compound. In certain embodiments, the compound is single-stranded. In certain embodiments, the compound is double-stranded. In certain embodiments, the modified oligonucleotide consists of 10 to 30 linked nucleosides. 
     Certain embodiments provide a compound comprising a modified oligonucleotide consisting of 10 to 80 linked nucleosides and having a nucleobase sequence comprising at least 10 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. In certain embodiments, the compound is an antisense compound or oligomeric compound. In certain embodiments, the compound is single-stranded. In certain embodiments, the compound is double-stranded. In certain embodiments, the modified oligonucleotide consists of 10 to 30 linked nucleosides. 
     Certain embodiments provide a compound comprising a modified oligonucleotide consisting of 11 to 80 linked nucleosides and having a nucleobase sequence comprising at least 11 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. In certain embodiments, the compound is an antisense compound or oligomeric compound. In certain embodiments, the compound is single-stranded. In certain embodiments, the compound is double-stranded. In certain embodiments, the modified oligonucleotide consists of 11 to 30 linked nucleosides. 
     Certain embodiments provide a compound comprising a modified oligonucleotide consisting of 12 to 80 linked nucleosides and having a nucleobase sequence comprising at least 12 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. In certain embodiments, the compound is an antisense compound or oligomeric compound. In certain embodiments, the compound is single-stranded. In certain embodiments, the compound is double-stranded. In certain embodiments, the modified oligonucleotide consists of 12 to 30 linked nucleosides. 
     Certain embodiments provide a compound comprising a modified oligonucleotide consisting of 16 to 80 linked nucleosides and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the compound is an antisense compound or oligomeric compound. In certain embodiments, the compound is single-stranded. In certain embodiments, the compound is double-stranded. In certain embodiments, the modified oligonucleotide consists of 16 to 30 linked nucleosides. 
     Certain embodiments provide a compound comprising a modified oligonucleotide consisting of 18 to 80 linked nucleosides and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the compound is an antisense compound or oligomeric compound. In certain embodiments, the compound is single-stranded. In certain embodiments, the compound is double-stranded. In certain embodiments, the modified oligonucleotide consists of 18 to 30 linked nucleosides. 
     Certain embodiments provide a compound comprising a modified oligonucleotide consisting of 20 to 80 linked nucleosides and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. In certain embodiments, the compound is an antisense compound or oligomeric compound. In certain embodiments, the compound is single-stranded. In certain embodiments, the compound is double-stranded. In certain embodiments, the modified oligonucleotide consists of 20 to 30 linked nucleosides. 
     Certain embodiments provide a compound comprising a modified oligonucleotide having a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 3-599. In certain embodiments, the compound is an antisense compound or oligomeric compound. In certain embodiments, the compound is single-stranded. In certain embodiments, the compound is double-stranded. 
     In certain embodiments, any of the foregoing modified oligonucleotides has at least one modified internucleoside linkage, at least one modified sugar, and/or at least one modified nucleobase. 
     In certain embodiments, at least one nucleoside of any of the foregoing modified oligonucleotides comprises a modified sugar. In certain embodiments, the modified sugar comprises a 2′-O-methoxyethyl group. In certain embodiments, the modified sugar is a bicyclic sugar, such as a 4′-CH(CH 3 )—O-2′ group, a 4′-CH 2 —O-2′ group, or a 4′-(CH 2 ) 2 —O-2′ group. 
     In certain embodiments, at least one internucleoside linkage of the modified oligonucleotide comprises a modified internucleoside linkage, such as a phosphorothioate internucleoside linkage. 
     In certain embodiments, at least one nucleobase of any of the foregoing modified oligonucleotides is a modified nucleobase, such as 5-methylcytosine. 
     In certain embodiments, any of the foregoing modified oligonucleotides has:
         a gap segment consisting of linked 2′-deoxynucleosides;   a 5′ wing segment consisting of linked nucleosides; and   a 3′ wing segment consisting of linked nucleosides;       

     wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar. In certain embodiments, the modified oligonucleotide consists of 16 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 16 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 16 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 18 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 18 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 18 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 20 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. In certain embodiments, the modified oligonucleotide consists of 20 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. In certain embodiments, the modified oligonucleotide consists of 20 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. 
     In certain embodiments, a compound comprises or consists of a modified oligonucleotide consisting of 16 to 80 linked nucleobases and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-599, wherein the modified oligonucleotide has:
         a gap segment consisting of linked 2′-deoxynucleosides;   a 5′ wing segment consisting of linked nucleosides; and   a 3′ wing segment consisting of linked nucleosides;       

     wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar. In certain embodiments, the modified oligonucleotide consists of 16 to 30 linked nucleosides. In certain embodiments, the modified oligonucleotide consists of 16 linked nucleosides. 
     In certain embodiments, a compound comprises or consists of a modified oligonucleotide consisting of 16 to 80 linked nucleobases and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470, wherein the modified oligonucleotide has: 
     a gap segment consisting of ten linked 2′-deoxynucleosides; 
     a 5′ wing segment consisting of three linked nucleosides; and 
     a 3′ wing segment consisting of three linked nucleosides; 
     wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment; wherein each nucleoside of each wing segment comprises a cEt nucleoside; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. In certain embodiments, the modified oligonucleotide consists of 16 to 30 linked nucleosides. In certain embodiments, the modified oligonucleotide consists of 16 linked nucleosides. 
     In certain embodiments, a compound comprises or consists of a modified oligonucleotide consisting of 18 to 80 linked nucleobases and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510, wherein each nucleoside of the modified oligonucleotide comprises a 2′-MOE nucleoside; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. In certain embodiments, the modified oligonucleotide consists of 18 to 30 linked nucleosides. In certain embodiments, the modified oligonucleotide consists of 18 linked nucleosides. 
     In certain embodiments, a compound comprises or consists of a modified oligonucleotide consisting of 20 to 80 linked nucleobases and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599, wherein each nucleoside of the modified oligonucleotide comprises a 2′-MOE nucleoside; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. In certain embodiments, the modified oligonucleotide consists of 20 to 30 linked nucleosides. In certain embodiments, the modified oligonucleotide consists of 20 linked nucleosides. 
     In certain embodiments, a compound comprises or consists of a modified oligonucleotide consisting of 16 linked nucleobases and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 549-588, wherein the modified oligonucleotide comprises the sugar motif: kddkddkddkddkddk in the 5′ to 3′ direction, wherein “k” indicates a cEt sugar moiety and “d” indicates an unmodified 2′-deoxyribosyl sugar moiety; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. 
     In certain embodiments, a compound comprises or consists of a modified oligonucleotide consisting of 16 linked nucleobases and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 549-588, wherein the modified oligonucleotide comprises the sugar motif: keekeekeekeekeek in the 5′ to 3′ direction, wherein “k” indicates a cEt sugar moiety and “e” indicates 2′-MOE sugar moiety; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. 
     In any of the foregoing embodiments, the compound or oligonucleotide can be at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% complementary to a SARS-CoV-2 RNA. 
     In certain embodiments, the modified oligonucleotide is described by its Compound Number or ION number in the Examples section below. 
     In any of the foregoing embodiments, the compound can be single-stranded. In certain embodiments, the compound comprises deoxyribonucleotides. In certain embodiments, the compound is double-stranded. In certain embodiments, the compound is double-stranded and comprises ribonucleotides. In any of the foregoing embodiments, the compound can be an antisense compound or oligomeric compound. 
     In any of the foregoing embodiments, the compound can consist of 8 to 80, 10 to 30, 12 to 50, 13 to 30, 13 to 50, 14 to 30, 14 to 50, 15 to 30, 15 to 50, 16 to 30, 16 to 50, 17 to 30, 17 to 50, 18 to 22, 18 to 24, 18 to 30, 18 to 50, 19 to 22, 19 to 30, 19 to 50, or 20 to 30 linked nucleosides. In certain embodiments, the compound comprises or consists of an oligonucleotide. 
     In certain embodiments, a compound is a modified oligonucleotide described by its Compound Number or ION number in the Examples section below. 
     In certain embodiments, compounds or compositions provided herein comprise a salt of the modified oligonucleotide. In certain embodiments, the salt is a sodium salt. In certain embodiments, the salt is a potassium salt. 
     Certain Indications 
     Certain embodiments provided herein relate to methods of inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load, which can be useful for preventing or treating COVID-19 in an individual, by administration of a compound that targets SARS-CoV-2 RNA. In certain embodiments, the compound can be an antisense compound, oligomeric compound, or oligonucleotide targeted to SARS-CoV-2 RNA. 
     In certain embodiments, a method of inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load, in lung cells comprises contacting lung cells with a compound comprising a SARS-CoV-2 specific inhibitor, thereby inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load in lung cells. In certain embodiments, the compound comprises an antisense compound targeted to SARS-CoV-2 RNA. In certain embodiments, the compound comprises an oligonucleotide targeted to SARS-CoV-2 RNA. In certain embodiments, the compound comprises a modified oligonucleotide consisting of 8 to 80 linked nucleosides and having a nucleobase sequence comprising at least 8 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. In certain embodiments, a compound comprises a modified oligonucleotide consisting of 16 to 80 linked nucleosides and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-599. In certain embodiments, a compound comprises a modified oligonucleotide having the nucleobase sequence of any one of SEQ ID NOs: 3-599. In certain embodiments, the modified oligonucleotide consists of 16 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 16 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 16 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 18 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 18 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 18 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 20 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. In certain embodiments, the modified oligonucleotide consists of 20 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. In certain embodiments, the modified oligonucleotide consists of 20 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. 
     In certain embodiments, a method of inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load, in an individual comprises administering to the individual a compound comprising a SARS-CoV-2 specific inhibitor, thereby preventing or treating COVID-19 in the individual. In certain embodiments, the compound comprises an antisense compound targeted to SARS-CoV-2 RNA. In certain embodiments, the compound comprises an oligonucleotide targeted to SARS-CoV-2 RNA. In certain embodiments, the compound comprises a modified oligonucleotide consisting of 8 to 80 linked nucleosides and having a nucleobase sequence comprising at least 8 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. In certain embodiments, a compound comprises a modified oligonucleotide consisting of 16 to 80 linked nucleosides and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-599. In certain embodiments, a compound comprises a modified oligonucleotide having the nucleobase sequence of any one of SEQ ID NOs: 3-599. In certain embodiments, the modified oligonucleotide consists of 16 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 16 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 16 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 18 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 18 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 18 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 20 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. In certain embodiments, the modified oligonucleotide consists of 20 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. In certain embodiments, the modified oligonucleotide consists of 20 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. 
     Certain embodiments are drawn to a compound comprising a SARS-CoV-2 specific inhibitor for use in inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load in lung cells or an individual. Certain embodiments are drawn to a compound comprising a SARS-CoV-2 specific inhibitor for use in preventing or treating COVID-19 in an individual. In certain embodiments, the compound comprises a modified oligonucleotide consisting of 8 to 80 linked nucleosides and having a nucleobase sequence comprising at least 8 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. In certain embodiments, a compound comprises a modified oligonucleotide consisting of 16 to 80 linked nucleosides and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-599. In certain embodiments, a compound comprises a modified oligonucleotide having the nucleobase sequence of any one of SEQ ID NOs: 3-599. In certain embodiments, the modified oligonucleotide consists of 16 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 16 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 16 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 18 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 18 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 18 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 20 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. In certain embodiments, the modified oligonucleotide consists of 20 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. In certain embodiments, the modified oligonucleotide consists of 20 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. 
     Certain embodiments are drawn to use of a compound comprising a SARS-CoV-2 specific inhibitor for the manufacture or preparation of a medicament for inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load in lung cells or an individual. Certain embodiments are drawn to a compound comprising a SARS-CoV-2 specific inhibitor for the manufacture or preparation of a medicament for preventing or treating COVID-19 in an individual. In certain embodiments, the compound comprises a modified oligonucleotide consisting of 8 to 80 linked nucleosides and having a nucleobase sequence comprising at least 8 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. In certain embodiments, a compound comprises a modified oligonucleotide consisting of 16 to 80 linked nucleosides and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-599. In certain embodiments, a compound comprises a modified oligonucleotide having the nucleobase sequence of any one of SEQ ID NOs: 3-599. In certain embodiments, the modified oligonucleotide consists of 16 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 16 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 16 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. In certain embodiments, the modified oligonucleotide consists of 18 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 18 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 18 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 471-510. In certain embodiments, the modified oligonucleotide consists of 20 to 80 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. In certain embodiments, the modified oligonucleotide consists of 20 to 30 linked nucleosides and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. In certain embodiments, the modified oligonucleotide consists of 20 linked nucleosides and has a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. 
     In any of the foregoing methods or uses, the compound can comprise or consist of a modified oligonucleotide consisting of 16 to 80 linked nucleobases and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-599, wherein the modified oligonucleotide has:
         a gap segment consisting of linked 2′-deoxynucleosides;   a 5′ wing segment consisting of linked nucleosides; and   a 3′ wing segment consisting of linked nucleosides;       

     wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar. In certain embodiments, the modified oligonucleotide consists of 16 to 30 linked nucleosides. In certain embodiments, the modified oligonucleotide consists of 16 linked nucleosides. 
     In any of the foregoing methods or uses, the compound can comprise or consist of a modified oligonucleotide consisting of 16 to 80 linked nucleobases and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470, wherein the modified oligonucleotide has: 
     a gap segment consisting of ten linked 2′-deoxynucleosides; 
     a 5′ wing segment consisting of three linked nucleosides; and 
     a 3′ wing segment consisting of three linked nucleosides; 
     wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment; wherein each nucleoside of each wing segment comprises a cEt nucleoside; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. In certain embodiments, the modified oligonucleotide consists of 16 to 30 linked nucleosides. In certain embodiments, the modified oligonucleotide consists of 16 linked nucleosides. 
     In any of the foregoing methods or uses, the compound can comprise or consist of a modified oligonucleotide consisting of 18 to 80 linked nucleobases and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510, wherein each nucleoside of the modified oligonucleotide comprises a 2′-MOE nucleoside; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. In certain embodiments, the modified oligonucleotide consists of 18 to 30 linked nucleosides. In certain embodiments, the modified oligonucleotide consists of 18 linked nucleosides. 
     In any of the foregoing methods or uses, the compound can comprise or consist of a modified oligonucleotide consisting of 20 to 80 linked nucleobases and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599, wherein each nucleoside of the modified oligonucleotide comprises a 2′-MOE nucleoside; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. In certain embodiments, the modified oligonucleotide consists of 20 to 30 linked nucleosides. In certain embodiments, the modified oligonucleotide consists of 20 linked nucleosides. 
     In any of the foregoing methods or uses, the compound can comprise or consist of a modified oligonucleotide consisting of 16 linked nucleobases and having a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 549-588, wherein the modified oligonucleotide comprises the sugar motif: kddkddkddkddkddk in the 5′ to 3′ direction, wherein “k” indicates a cEt sugar moiety and “d” indicates an unmodified 2′-deoxyribosyl sugar moiety; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. 
     In any of the foregoing methods or uses, the compound can comprise or consist of a modified oligonucleotide consisting of 16 linked nucleobases and having a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 549-588, wherein the modified oligonucleotide comprises the sugar motif: keekeekeekeekeek in the 5′ to 3′ direction, wherein “k” indicates a cEt sugar moiety and “e” indicates 2′-MOE sugar moiety; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. 
     In any of the foregoing methods or uses, the compound can be targeted to SARS-CoV-2 RNA. In certain embodiments, the compound comprises or consists of a modified oligonucleotide, for example a modified oligonucleotide consisting of 8 to 80 linked nucleosides, 10 to 30 linked nucleosides in length, 12 to 30 linked nucleosides in length, or 20 linked nucleosides in length. In certain embodiments, the modified oligonucleotide is at least 80%, 85%, 90%, 95% or 100% complementary to any of the nucleobase sequences recited in SEQ ID NO: 1 or 2. In certain embodiments, the modified oligonucleotide comprises at least one modified internucleoside linkage, at least one modified sugar and/or at least one modified nucleobase. In certain embodiments, the modified internucleoside linkage is a phosphorothioate internucleoside linkage, the modified sugar is a bicyclic sugar or a 2′-O-methoxyethyl, and the modified nucleobase is a 5-methylcytosine. In certain embodiments, the modified oligonucleotide comprises a gap segment consisting of linked 2′-deoxynucleosides; a 5′ wing segment consisting of linked nucleosides; and a 3′ wing segment consisting of linked nucleosides, wherein the gap segment is positioned immediately adjacent to and between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar. 
     In any of the foregoing methods or uses, the modified oligonucleotide can be 12 to 30, 15 to 30, 15 to 25, 15 to 24, 16 to 24, 17 to 24, 18 to 24, 19 to 24, 20 to 24, 19 to 22, 20 to 22, 16 to 20, or 17 or 20 linked nucleosides in length. In certain embodiments, the modified oligonucleotide is at least 80%, 85%, 90%, 95% or 100% complementary to any of the nucleobase sequences recited in SEQ ID NO: 1 or 2. In certain embodiments, the modified oligonucleotide comprises at least one modified internucleoside linkage, at least one modified sugar and/or at least one modified nucleobase. In certain embodiments, the modified internucleoside linkage is a phosphorothioate internucleoside linkage, the modified sugar is a bicyclic sugar or a 2′-O-methoxyethyl, and the modified nucleobase is a 5-methylcytosine. In certain embodiments, the modified oligonucleotide comprises a gap segment consisting of linked 2′-deoxynucleosides; a 5′ wing segment consisting of linked nucleosides; and a 3′ wing segment consisting of linked nucleosides, wherein the gap segment is positioned immediately adjacent to and between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar. 
     In any of the foregoing methods or uses, the modified oligonucleotide can be one that is described by its Compound Number or ION number in the Examples section below. 
     In any of the foregoing methods or uses, the compound can be administered in an aerosol form. In any of the foregoing methods or uses, the compound can be administered to the lungs of a patient. In any of the foregoing methods or uses, the compound can be administered by inhalation. In any of the foregoing methods or uses, the compound can be administered by an inhaler. In any of the foregoing methods or uses, the compound can be administered by a nebulizer. 
     Certain Numbered Embodiments 
     The following are certain numbered embodiments that are not limiting on any other embodiments described herein: 
     Embodiment 1. A compound comprising a modified oligonucleotide consisting of 8 to 80 linked nucleosides and having a nucleobase sequence comprising at least 8 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. 
     Embodiment 2. A compound comprising a modified oligonucleotide consisting of 9 to 80 linked nucleosides and having a nucleobase sequence comprising at least 9 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. 
     Embodiment 3. A compound comprising a modified oligonucleotide consisting of 10 to 80 linked nucleosides and having a nucleobase sequence comprising at least 10 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. 
     Embodiment 4. A compound comprising a modified oligonucleotide consisting of 11 to 80 linked nucleosides and having a nucleobase sequence comprising at least 11 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. 
     Embodiment 5. A compound comprising a modified oligonucleotide consisting of 12 to 80 linked nucleosides and having a nucleobase sequence comprising at least 12 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 3-599. 
     Embodiment 6. A compound comprising a modified oligonucleotide consisting of 16 to 80 linked nucleosides and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470 or 549-588. 
     Embodiment 7. A compound comprising a modified oligonucleotide consisting of 18 to 80 linked nucleosides and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510. 
     Embodiment 8. A compound comprising a modified oligonucleotide consisting of 20 to 80 linked nucleosides and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599. 
     Embodiment 9. A compound comprising a modified oligonucleotide having a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 3-599. 
     Embodiment 10. The compound of any one of embodiments 1-9, wherein at least one internucleoside linkage of the modified oligonucleotide is a modified internucleoside linkage, at least one nucleoside of the modified oligonucleotide comprises a modified sugar, or at least one nucleobase of the modified oligonucleotide is a modified nucleobase. 
     Embodiment 11. The compound of embodiment 10, wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage. 
     Embodiment 12. The compound of embodiment 10 or 11, wherein the modified sugar is a bicyclic sugar. 
     Embodiment 13. The compound of embodiment 12, wherein the bicyclic sugar is selected from the group consisting of: 4′-(CH 2 )—O-2′ (LNA); 4′-(CH 2 ) 2 —O-2′ (ENA); and 4′-CH(CH 3 )—O-2′ (cEt). 
     Embodiment 14. The compound of embodiment 10 or 11, wherein the modified sugar is 2′-O-methoxyethyl. 
     Embodiment 15. The compound of any one of embodiments 10-14, wherein the modified nucleobase is a 5-methylcytosine. 
     Embodiment 16. The compound of any one of embodiments 1-15, wherein the modified oligonucleotide has:
         a gap segment consisting of linked 2′-deoxynucleosides;   a 5′ wing segment consisting of linked nucleosides; and   a 3′ wing segment consisting of linked nucleosides;       

     wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar. 
     Embodiment 17. A modified oligonucleotide consisting of 16 to 80 linked nucleobases and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 3-470, wherein the modified oligonucleotide has:
         a gap segment consisting of ten linked 2′-deoxynucleosides;   a 5′ wing segment consisting of three linked nucleosides; and   a 3′ wing segment consisting of three linked nucleosides;       

     wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment; wherein each nucleoside of each wing segment comprises a cEt nucleoside; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. 
     Embodiment 18. A modified oligonucleotide consisting of 18 to 80 linked nucleobases and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 471-510, wherein each nucleoside of the modified oligonucleotide comprises a 2′-MOE nucleoside; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. 
     Embodiment 19. A modified oligonucleotide consisting of 20 to 80 linked nucleobases and having a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOs: 511-548 or 589-599, wherein each nucleoside of the modified oligonucleotide comprises a 2′-MOE nucleoside; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. 
     Embodiment 20. A modified oligonucleotide consisting of 16 linked nucleobases and having a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 549-588, wherein the modified oligonucleotide comprises the sugar motif: kddkddkddkddkddk in the 5′ to 3′ direction, wherein wherein “k” indicates a cEt sugar moiety and “d” indicates an unmodified 2′-deoxyribosyl sugar moiety; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. 
     Embodiment 21. A modified oligonucleotide consisting of 16 linked nucleobases and having a nucleobase sequence consisting of the nucleobase sequence of any one of SEQ ID NOs: 549-588, wherein the modified oligonucleotide comprises the sugar motif: keekeekeekeekeek in the 5′ to 3′ direction, wherein wherein “k” indicates a cEt sugar moiety and “e” indicates 2′-MOE sugar moiety; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. 
     Embodiment 22. The compound of any one of embodiments 1-21, wherein the oligonucleotide is at least 80%, 85%, 90%, 95% or 100% complementary to SEQ ID NO:1 or 2. 
     Embodiment 23. The compound of any one of embodiments 1-22, wherein the compound is single-stranded. 
     Embodiment 24. The compound of any one of embodiments 1-22, wherein the compound is double-stranded. 
     Embodiment 25. The compound of any one of embodiments 1-22, wherein the compound comprises ribonucleotides. 
     Embodiment 26. The compound of any one of embodiments 1-22, wherein the compound comprises deoxyribonucleotides. 
     Embodiment 27. The compound of any one of embodiments 1-21, wherein the modified oligonucleotide consists of 16 to 30 linked nucleosides or 18 to 30 linked nucleosides, or 20 to 30 linked nucleosides. 
     Embodiment 28. The compound of any one of embodiments 1-27, wherein the compound consists of the modified oligonucleotide. 
     Embodiment 29. A compound consisting of a pharmaceutically acceptable salt of any of the compounds of embodiments 1-28. 
     Embodiment 30. The compound of embodiment 29, wherein the pharmaceutically acceptable salt is a sodium salt. 
     Embodiment 31. The compound of embodiment 30, wherein the pharmaceutically acceptable salt is a potassium salt. 
     Embodiment 32. A composition comprising the compound of any one of embodiments 1-31 and a pharmaceutically acceptable diluent or carrier. 
     Embodiment 33. A composition comprising the compound of any one of embodiments 1-31 and water. 
     Embodiment 34. A composition comprising a compound of any one of embodiments 1-32, for use in therapy. 
     Embodiment 35. A method of inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load in lung cells comprising contacting the lung cells with the compound of any one of embodiments 1-31 or composition of any one of embodiments 32-34, thereby inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load in the lung cells. 
     Embodiment 36. A method of inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load in an individual comprising administering to the individual the compound of any one of embodiments 1-31 or composition of any one of embodiments 32-34, thereby inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load in the individual. 
     Embodiment 37. A method of preventing or treating COVID-19 in an individual comprising administering to the individual the compound of any one of embodiments 1-31 or composition of any one of embodiments 32-34, thereby preventing or treating COVID-19 in the individual. 
     Embodiment 38. The method of any of embodiments 35-37, wherein contacting or administering the compound of any one of embodiments 1-31 or composition of any one of embodiments 32-34 prevents or improves a COVID-19 symptom. 
     Embodiment 39. The method of embodiment 38, wherein the COVID symptom is respiratory illness, difficulty breathing, fever, cough, fatigue, aches and pains, sore throat, runny nose, diarrhea, loss of taste or smell, or nasal congestion. 
     Embodiment 40. Use of the compound of any one of embodiments 1-31 or composition of any one of embodiments 32-34 for inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load in lung cells. 
     Embodiment 41. Use of the compound of any one of embodiments 1-31 or composition of any one of embodiments 32-34 for inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load in an individual. 
     Embodiment 42. Use of the compound of any one of embodiments 1-31 or composition of any one of embodiments 32-34 for preventing or treating COVID-19 in an individual. 
     Embodiment 43. The use of any of embodiments 40-42, for preventing or improving a COVID-19 symptom. 
     Embodiment 44. The use of embodiment 43, wherein the COVID symptom is respiratory illness, difficulty breathing, fever, cough, fatigue, aches and pains, sore throat, runny nose, diarrhea, loss of taste or smell, or nasal congestion. 
     Embodiment 45. Use of the compound of any one of embodiments 1-31 or composition of any one of embodiments 32-34 for the preparation or manufacture of a medicament for inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load in lung cells. 
     Embodiment 46. Use of the compound of any one of embodiments 1-31 or composition of any one of embodiments 32-34 for the preparation or manufacture of a medicament for inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load in an individual. 
     Embodiment 47. Use of the compound of any one of embodiments 1-31 or composition of any one of embodiments 32-34 for the preparation or manufacture of a medicament for preventing or treating COVID-19 in an individual. 
     Embodiment 48. The use of any of embodiments 40-42, for the preparation or manufacture of a medicament for preventing or improving a COVID-19 symptom. 
     Embodiment 49. The use of embodiment 43, wherein the COVID symptom is respiratory illness, difficulty breathing, fever, cough, fatigue, aches and pains, sore throat, runny nose, diarrhea, loss of taste or smell, or nasal congestion. 
     Certain Combinations 
     In certain embodiments, a first agent comprising a compound described herein is co-administered with one or more secondary agents. In certain embodiments, such second agents are designed to treat the same disease, disorder, or condition as the first agent described herein. In certain embodiments, such second agents are designed to treat a different disease, disorder, or condition as the first agent described herein. In certain embodiments, a first agent is designed to treat an undesired side effect of a second agent. In certain embodiments, second agents are co-administered with the first agent to treat an undesired effect of the first agent. In certain embodiments, such second agents are designed to treat an undesired side effect of one or more pharmaceutical compositions as described herein. In certain embodiments, second agents are co-administered with the first agent to produce a combinational effect. In certain embodiments, second agents are co-administered with the first agent to produce a synergistic effect. In certain embodiments, the co-administration of the first and second agents permits use of lower dosages than would be required to achieve a therapeutic or prophylactic effect if the agents were administered as independent therapy. 
     In certain embodiments, one or more compounds or compositions provided herein are co-administered with one or more secondary agents. In certain embodiments, one or more compounds or compositions provided herein and one or more secondary agents, are administered at different times. In certain embodiments, one or more compounds or compositions provided herein and one or more secondary agents, are prepared together in a single formulation. In certain embodiments, one or more compounds or compositions provided herein and one or more secondary agents, are prepared separately. In certain embodiments, a secondary agent can be one or more of the following: remdesivir, hydroxychloroquine, chloroquine, azithromycin, and/or ivermectin. 
     Certain Compounds 
     In certain embodiments, compounds described herein can be antisense compounds. In certain embodiments, the antisense compound comprises or consists of an oligomeric compound. In certain embodiments, the oligomeric compound comprises a modified oligonucleotide. In certain embodiments, the modified oligonucleotide has a nucleobase sequence complementary to that of a target nucleic acid. 
     In certain embodiments, a compound described herein comprises or consists of a modified oligonucleotide. In certain embodiments, the modified oligonucleotide has a nucleobase sequence complementary to that of a target nucleic acid. 
     In certain embodiments, a compound or antisense compound is single-stranded. Such a single-stranded compound or antisense compound comprises or consists of an oligomeric compound. In certain embodiments, such an oligomeric compound comprises or consists of an oligonucleotide and optionally a conjugate group. In certain embodiments, the oligonucleotide is an antisense oligonucleotide. In certain embodiments, the oligonucleotide is modified. In certain embodiments, the oligonucleotide of a single-stranded antisense compound or oligomeric compound comprises a self-complementary nucleobase sequence. 
     In certain embodiments, compounds are double-stranded. Such double-stranded compounds comprise a first modified oligonucleotide having a region complementary to a target nucleic acid and a second modified oligonucleotide having a region complementary to the first modified oligonucleotide. In certain embodiments, the modified oligonucleotide is an RNA oligonucleotide. In such embodiments, the thymine nucleobase in the modified oligonucleotide is replaced by a uracil nucleobase. In certain embodiments, compound comprises a conjugate group. In certain embodiments, one of the modified oligonucleotides is conjugated. In certain embodiments, both the modified oligonucleotides are conjugated. In certain embodiments, the first modified oligonucleotide is conjugated. In certain embodiments, the second modified oligonucleotide is conjugated. In certain embodiments, the first modified oligonucleotide is 12-30 linked nucleosides in length and the second modified oligonucleotide is 12-30 linked nucleosides in length. In certain embodiments, one of the modified oligonucleotides has a nucleobase sequence comprising at least 8 contiguous nucleobases of any of SEQ ID NOs: 3-599. 
     In certain embodiments, antisense compounds are double-stranded. Such double-stranded antisense compounds comprise a first oligomeric compound having a region complementary to a target nucleic acid and a second oligomeric compound having a region complementary to the first oligomeric compound. The first oligomeric compound of such double stranded antisense compounds typically comprises or consists of a modified oligonucleotide and optionally a conjugate group. The oligonucleotide of the second oligomeric compound of such double-stranded antisense compound may be modified or unmodified. Either or both oligomeric compounds of a double-stranded antisense compound may comprise a conjugate group. The oligomeric compounds of double-stranded antisense compounds may include non-complementary overhanging nucleosides. 
     Examples of single-stranded and double-stranded compounds include but are not limited to oligonucleotides, siRNAs, microRNA targeting oligonucleotides, and single-stranded RNAi compounds, such as small hairpin RNAs (shRNAs), single-stranded siRNAs (ssRNAs), and microRNA mimics. 
     In certain embodiments, a compound described herein has a nucleobase sequence that, when written in the 5′ to 3′ direction, comprises the reverse complement of the target segment of a target nucleic acid to which it is targeted. 
     In certain embodiments, a compound described herein comprises an oligonucleotide 10 to 30 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 12 to 30 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 12 to 22 linked subunits in length. In certain embodiments, compound described herein comprises an oligonucleotide 14 to 30 linked subunits in length. In certain embodiments, compound described herein comprises an oligonucleotide 14 to 20 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 15 to 30 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 15 to 20 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 16 to 30 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 16 to 20 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 17 to 30 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 17 to 20 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 18 to 30 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 18 to 21 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 18 to 20 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 20 to 30 linked subunits in length. In other words, such oligonucleotides are 12 to 30 linked subunits, 14 to 30 linked subunits, 14 to 20 subunits, 15 to 30 subunits, 15 to 20 subunits, 16 to 30 subunits, 16 to 20 subunits, 17 to 30 subunits, 17 to 20 subunits, 18 to 30 subunits, 18 to 20 subunits, 18 to 21 subunits, 20 to 30 subunits, or 12 to 22 linked subunits in length, respectively. In certain embodiments, a compound described herein comprises an oligonucleotide 14 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 16 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 17 linked subunits in length. In certain embodiments, compound described herein comprises an oligonucleotide 18 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 19 linked subunits in length. In certain embodiments, a compound described herein comprises an oligonucleotide 20 linked subunits in length. In other embodiments, a compound described herein comprises an oligonucleotide 8 to 80, 12 to 50, 13 to 30, 13 to 50, 14 to 30, 14 to 50, 15 to 30, 15 to 50, 16 to 30, 16 to 50, 17 to 30, 17 to 50, 18 to 22, 18 to 24, 18 to 30, 18 to 50, 19 to 22, 19 to 30, 19 to 50, or 20 to 30 linked subunits. In certain such embodiments, the compound described herein comprises an oligonucleotide 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80 linked subunits in length, or a range defined by any two of the above values. In some embodiments the linked subunits are nucleotides, nucleosides, or nucleobases. 
     In certain embodiments, the compound may further comprise additional features or elements, such as a conjugate group, that are attached to the oligonucleotide. In certain embodiments, such compounds are antisense compounds. In certain embodiments, such compounds are oligomeric compounds. In embodiments where a conjugate group comprises a nucleoside (i.e. a nucleoside that links the conjugate group to the oligonucleotide), the nucleoside of the conjugate group is not counted in the length of the oligonucleotide. 
     In certain embodiments, compounds may be shortened or truncated. For example, a single subunit may be deleted from the 5′ end (5′ truncation), or alternatively from the 3′ end (3′ truncation). A shortened or truncated compound targeted to an SARS-CoV-2 RNA may have two subunits deleted from the 5′ end, or alternatively may have two subunits deleted from the 3′ end, of the compound. Alternatively, the deleted nucleosides may be dispersed throughout the compound. 
     When a single additional subunit is present in a lengthened compound, the additional subunit may be located at the 5′ or 3′ end of the compound. When two or more additional subunits are present, the added subunits may be adjacent to each other, for example, in a compound having two subunits added to the 5′ end (5′ addition), or alternatively to the 3′ end (3′ addition), of the compound. Alternatively, the added subunits may be dispersed throughout the compound. 
     It is possible to increase or decrease the length of a compound, such as an oligonucleotide, and/or introduce mismatch bases without eliminating activity (Woolf et al.  Proc. Natl. Acad. Sci. USA  1992, 89:7305-7309; Gautschi et al.  J. Natl. Cancer Inst . March 2001, 93:463-471; Maher and Dolnick  Nuc. Acid. Res.  1998, 16:3341-3358). However, seemingly small changes in oligonucleotide sequence, chemistry and motif can make large differences in one or more of the many properties required for clinical development (Seth et al.  J. Med. Chem.  2009, 52, 10; Egli et al.  J. Am. Chem. Soc.  2011, 133, 16642). 
     In certain embodiments, compounds described herein are interfering RNA compounds (RNAi), which include double-stranded RNA compounds (also referred to as short-interfering RNA or siRNA) and single-stranded RNAi compounds (or ssRNA). Such compounds work at least in part through the RISC pathway to degrade and/or sequester a target nucleic acid (thus, include microRNA/microRNA-mimic compounds). As used herein, the term siRNA is meant to be equivalent to other terms used to describe nucleic acid molecules that are capable of mediating sequence specific RNAi, for example short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), short hairpin RNA (shRNA), short interfering oligonucleotide, short interfering nucleic acid, short interfering modified oligonucleotide, chemically modified siRNA, post-transcriptional gene silencing RNA (ptgsRNA), and others. In addition, as used herein, the term “RNAi” is meant to be equivalent to other terms used to describe sequence specific RNA interference, such as post transcriptional gene silencing, translational inhibition, or epigenetics. 
     In certain embodiments, a compound described herein can comprise any of the oligonucleotide sequences targeted to SARS-CoV-2 RNA described herein. In certain embodiments, the compound can be double-stranded. In certain embodiments, the compound comprises a first strand comprising at least an 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 contiguous nucleobase portion of any one of SEQ ID NOs: 3-599 and a second strand. In certain embodiments, the compound comprises a first strand comprising the nucleobase sequence of any one of SEQ ID NOs: 3-599 and a second strand. In certain embodiments, the compound comprises ribonucleotides in which the first strand has uracil (U) in place of thymine (T) in any one of SEQ ID NOs: 3-599. In certain embodiments, the compound comprises (i) a first strand comprising a nucleobase sequence complementary to the site on SARS-CoV-2 RNA to which any of SEQ ID NOs: 3-599 is targeted, and (ii) a second strand. In certain embodiments, the compound comprises one or more modified nucleotides in which the 2′ position in the sugar contains a halogen (such as fluorine group; 2′-F) or contains an alkoxy group (such as a methoxy group; 2′-OMe). In certain embodiments, the compound comprises at least one 2′-F sugar modification and at least one 2′-OMe sugar modification. In certain embodiments, the at least one 2′-F sugar modification and at least one 2′-OMe sugar modification are arranged in an alternating pattern for at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 contiguous nucleobases along a strand of the dsRNA compound. In certain embodiments, the compound comprises one or more linkages between adjacent nucleotides other than a naturally-occurring phosphodiester linkage. Examples of such linkages include phosphoramide, phosphorothioate, and phosphorodithioate linkages. The compounds may also be chemically modified nucleic acid molecules as taught in U.S. Pat. No. 6,673,661. In other embodiments, the compound contains one or two capped strands, as disclosed, for example, by WO 00/63364, filed Apr. 19, 2000. 
     In certain embodiments, the first strand of the compound is an siRNA guide strand and the second strand of the compound is an siRNA passenger strand. In certain embodiments, the second strand of the compound is complementary to the first strand. In certain embodiments, each strand of the compound is 16, 17, 18, 19, 20, 21, 22, or 23 linked nucleosides in length. In certain embodiments, the first or second strand of the compound can comprise a conjugate group. 
     In certain embodiments, a compound described herein can comprise any of the oligonucleotide sequences targeted to SARS-CoV-2 RNA described herein. In certain embodiments, the compound is single stranded. In certain embodiments, such a compound is a single-stranded RNAi (ssRNAi) compound. In certain embodiments, the compound comprises at least an 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 contiguous nucleobase portion of any one of SEQ ID NOs: 3-599. In certain embodiments, the compound comprises the nucleobase sequence of any one of SEQ ID NOs: 3-599. In certain embodiments, the compound comprises ribonucleotides in which uracil (U) is in place of thymine (T) in any one of SEQ ID NOs: 3-599. In certain embodiments, the compound comprises a nucleobase sequence complementary to the site on SARS-CoV-2 RNA to which any of SEQ ID NOs: 3-599 is targeted. In certain embodiments, the compound comprises one or more modified nucleotides in which the 2′ position in the sugar contains a halogen (such as fluorine group; 2′-F) or contains an alkoxy group (such as a methoxy group; 2′-OMe). In certain embodiments, the compound comprises at least one 2′-F sugar modification and at least one 2′-OMe sugar modification. In certain embodiments, the at least one 2′-F sugar modification and at least one 2′-OMe sugar modification are arranged in an alternating pattern for at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 contiguous nucleobases along a strand of the compound. In certain embodiments, the compound comprises one or more linkages between adjacent nucleotides other than a naturally-occurring phosphodiester linkage. Examples of such linkages include phosphoramide, phosphorothioate, and phosphorodithioate linkages. The compounds may also be chemically modified nucleic acid molecules as taught in U.S. Pat. No. 6,673,661. In other embodiments, the compound contains a capped strand, as disclosed, for example, by WO 00/63364, filed Apr. 19, 2000. In certain embodiments, the compound consists of 16, 17, 18, 19, 20, 21, 22, or 23 linked nucleosides. In certain embodiments, the compound can comprise a conjugate group. 
     In certain embodiments, compounds described herein comprise modified oligonucleotides. Certain modified oligonucleotides have one or more asymmetric center and thus give rise to enantiomers, diastereomers, and other stereoisomeric configurations that may be defined, in terms of absolute stereochemistry, as (R) or (S), as α or β such as for sugar anomers, or as (D) or (L) such as for amino acids etc. Included in the modified oligonucleotides provided herein are all such possible isomers, including their racemic and optically pure forms, unless specified otherwise. Likewise, all cis- and trans-isomers and tautomeric forms are also included. 
     The compounds described herein include variations in which one or more atoms are replaced with a non-radioactive isotope or radioactive isotope of the indicated element. For example, compounds herein that comprise hydrogen atoms encompass all possible deuterium substitutions for each of the  1 H hydrogen atoms. Isotopic substitutions encompassed by the compounds herein include but are not limited to:  2 H or  3 H in place of  1 H,  13 C or  14 C in place of  12 C,  15 N in place of  14 N,  17 O or  18 O in place of  16 O, and  33 S,  34 S,  35 S, or  36 S in place of  32 S. In certain embodiments, non-radioactive isotopic substitutions may impart new properties on the compound that are beneficial for use as a therapeutic or research tool. In certain embodiments, radioactive isotopic substitutions may make the compound suitable for research or diagnostic purposes, such as an imaging assay. 
     Certain Mechanisms 
     In certain embodiments, compounds described herein comprise or consist of modified oligonucleotides. In certain embodiments, compounds described herein are antisense compounds. In certain embodiments, compounds comprise oligomeric compounds. In certain embodiments, compounds described herein are capable of hybridizing to a target nucleic acid, resulting in at least one antisense activity. In certain embodiments, compounds described herein selectively affect one or more target nucleic acid. Such compounds comprise a nucleobase sequence that hybridizes to one or more target nucleic acid, resulting in one or more desired antisense activity and does not hybridize to one or more non-target nucleic acid or does not hybridize to one or more non-target nucleic acid in such a way that results in a significant undesired antisense activity. 
     In certain antisense activities, hybridization of a compound described herein to a target nucleic acid results in recruitment of a protein that cleaves the target nucleic acid. For example, certain compounds described herein result in RNase H mediated cleavage of the target nucleic acid. RNase H is a cellular endonuclease that cleaves the RNA strand of an RNA:DNA duplex. The DNA in such an RNA:DNA duplex need not be unmodified DNA. In certain embodiments, compounds described herein are sufficiently “DNA-like” to elicit RNase H activity. Further, in certain embodiments, one or more non-DNA-like nucleoside in the gap of a gapmer is tolerated. 
     In certain antisense activities, compounds described herein or a portion of the compound is loaded into an RNA-induced silencing complex (RISC), ultimately resulting in cleavage of the target nucleic acid. For example, certain compounds described herein result in cleavage of the target nucleic acid by Argonaute. Compounds that are loaded into RISC are RNAi compounds. RNAi compounds may be double-stranded (siRNA) or single-stranded (ssRNA). 
     In certain embodiments, hybridization of compounds described herein to a target nucleic acid does not result in recruitment of a protein that cleaves that target nucleic acid. In certain such embodiments, hybridization of the compound to the target nucleic acid results in alteration of splicing of the target nucleic acid. In certain embodiments, hybridization of the compound to a target nucleic acid results in inhibition of a binding interaction between the target nucleic acid and a protein or other nucleic acid. In certain such embodiments, hybridization of the compound to a target nucleic acid results in alteration of translation of the target nucleic acid. 
     Antisense activities may be observed directly or indirectly. In certain embodiments, observation or detection of an antisense activity involves observation or detection of a change in an amount of a target nucleic acid or protein encoded by such target nucleic acid, a change in the ratio of splice variants of a nucleic acid or protein, and/or a phenotypic change in a cell or animal. 
     Target Nucleic Acids. Target Regions and Nucleotide Sequences 
     In certain embodiments, compounds described herein comprise or consist of an oligonucleotide comprising a region that is complementary to a SARS-CoV-2 RNA sequence. 
     SARS-CoV-2 RNA sequences include, without limitation, the following Genbank Accession Nos., each of which is incorporated by reference in its entirety: NC_045512.2 (designated herein as SEQ ID NO: 1); the complement of NC_045512.2 (designated herein as SEQ ID NO: 2); NC_045512, MT350234, MT350236, MT350237, MT350238, MT350239, MT350240, MT350241, MT350242, MT350243, MT350244, MT350245, MT350246, MT350247, MT350248, MT350249, MT350250, MT350251, MT350252, MT350253, MT350254, MT350255, MT350256, MT350257, MT350263, MT350264, MT350265, MT350266, MT350267, MT350268, MT350269, MT350270, MT350271, MT350272, MT350273, MT350274, MT350275, MT350276, MT350277, MT350278, MT350279, MT350280, MT350282, MT344135, MT344944, MT344945, MT344946, MT344947, MT344948, MT344949, MT344950, MT344951, MT344952, MT344953, MT344954, MT344955, MT344956, MT344957, MT344958, MT344959, MT344960, MT344961, MT344962, MT344963, MT345798, MT345799, MT345800, MT345801, MT345802, MT345803, MT345804, MT345805, MT345806, MT345807, MT345808, MT345809, MT345810, MT345811, MT345812, MT345813, MT345814, MT345815, MT345816, MT345817, MT345818, MT345819, MT345820, MT345821, MT345822, MT345823, MT345824, MT345825, MT345826, MT345827, MT345828, MT345829, MT345830, MT345831, MT345832, MT345833, MT345834, MT345835, MT345836, MT345837, MT345838, MT345839, MT345840, MT345841, MT345842, MT345843, MT345844, MT345845, MT345846, MT345847, MT345848, MT345849, MT345850, MT345851, MT345852, MT345853, MT345854, MT345855, MT345856, MT345857, MT345858, MT345859, MT345860, MT345861, MT345862, MT345863, MT345864, MT345865, MT345866, MT345867, MT345868, MT345869, MT345870, MT345871, MT345872, MT345873, MT345874, MT345875, MT345876, MT345877, MT345878, MT345879, MT345880, MT345881, MT345882, MT345883, MT345884, MT345885, MT345886, MT345887, MT345888, MT339039, MT339040, MT339041, MT334522, MT334523, MT334524, MT334525, MT334526, MT334527, MT334528, MT334529, MT334530, MT334531, MT334532, MT334533, MT334534, MT334535, MT334536, MT334537, MT334538, MT334539, MT334540, MT334541, MT334542, MT334543, MT334544, MT334545, MT334546, MT334547, MT334548, MT334549, MT334550, MT334551, MT334552, MT334553, MT334554, MT334555, MT334556, MT334557, MT334558, MT334559, MT334560, MT334561, MT334562, MT334563, MT334564, MT334565, MT334566, MT334567, MT334568, MT334569, MT334570, MT334571, MT334572, MT334573, MT324062, MT324679, MT324680, MT324681, MT324682, MT324683, MT324684, MT325561, MT325562, MT325563, MT325564, MT325565, MT325566, MT325567, MT325568, MT325569, MT325570, MT325571, MT325572, MT325573, MT325574, MT325575, MT325576, MT325577, MT325578, MT325579, MT325580, MT325581, MT325582, MT325583, MT325584, MT325585, MT325586, MT325587, MT325588, MT325589, MT325590, MT325591, MT325592, MT325593, MT325594, MT325595, MT325596, MT325597, MT325598, MT325599, MT325600, MT325601, MT325602, MT325603, MT325604, MT325605, MT325606, MT325607, MT325608, MT325609, MT325610, MT325611, MT325612, MT325613, MT325614, MT325615, MT325616, MT325617, MT325618, MT325619, MT325620, MT325621, MT325622, MT325623, MT325624, MT325625, MT325626, MT325627, MT325628, MT325629, MT325630, MT325631, MT325632, MT325633, MT325634, MT325635, MT325636, MT325637, MT325638, MT325639, MT325640, MT326023, MT326024, MT326025, MT326026, MT326027, MT326028, MT326029, MT326030, MT326031, MT326032, MT326033, MT326034, MT326035, MT326036, MT326037, MT326038, MT326039, MT326040, MT326041, MT326042, MT326043, MT326044, MT326045, MT326046, MT326047, MT326048, MT326049, MT326050, MT326051, MT326052, MT326053, MT326054, MT326055, MT326056, MT326057, MT326058, MT326059, MT326060, MT326061, MT326062, MT326063, MT326064, MT326065, MT326066, MT326067, MT326068, MT326069, MT326070, MT326071, MT326072, MT326073, MT326074, MT326075, MT326076, MT326077, MT326078, MT326079, MT326080, MT326081, MT326082, MT326083, MT326084, MT326085, MT326086, MT326087, MT326088, MT326089, MT326090, MT326091, MT326092, MT326093, MT326094, MT326095, MT326096, MT326097, MT326098, MT326099, MT326100, MT326101, MT326102, MT326103, MT326104, MT326105, MT326106, MT326107, MT326108, MT326109, MT326110, MT326111, MT326112, MT326113, MT326114, MT326115, MT326116, MT326117, MT326118, MT326119, MT326120, MT326121, MT326122, MT326123, MT326124, MT326125, MT326126, MT326127, MT326128, MT326129, MT326130, MT326131, MT326132, MT326133, MT326134, MT326135, MT326136, MT326137, MT326138, MT326139, MT326140, MT326141, MT326142, MT326143, MT326144, MT326145, MT326146, MT326147, MT326148, MT326149, MT326150, MT326151, MT326152, MT326153, MT326154, MT326155, MT326156, MT326157, MT326158, MT326159, MT326160, MT326161, MT326162, MT326163, MT326164, MT326165, MT326166, MT326167, MT326168, MT326169, MT326170, MT326171, MT326172, MT326173, MT326174, MT326175, MT326176, MT326177, MT326178, MT326179, MT326180, MT326181, MT326182, MT326183, MT326184, MT326185, MT326186, MT326187, MT326188, MT326189, MT326190, MT326191, MT327745, MT328032, MT328033, MT328034, MT328035, MT039874, MT077125, MT322394, MT322395, MT322396, MT322397, MT322398, MT322399, MT322400, MT322401, MT322402, MT322403, MT322404, MT322405, MT322406, MT322407, MT322408, MT322409, MT322410, MT322411, MT322412, MT322413, MT322414, MT322415, MT322416, MT322417, MT322418, MT322419, MT322420, MT322421, MT322422, MT322423, MT322424, MT320538, MT320891, MT308692, MT308693, MT308694, MT308695, MT308696, MT308697, MT308698, MT308699, MT308700, MT308701, MT308702, MT308703, MT308704, MT293547, MT300186, MT304474, MT304475, MT304476, MT304477, MT304478, MT304479, MT304480, MT304481, MT304482, MT304483, MT304484, MT304485, MT304486, MT304487, MT304488, MT304489, MT304490, MT304491, MT273658, MT281530, MT281577, MT291826, MT291827, MT291828, MT291829, MT291830, MT291831, MT291832, MT291833, MT291834, MT291835, MT291836, MT292569, MT292570, MT292571, MT292572, MT292573, MT292574, MT292575, MT292576, MT292577, MT292578, MT292579, MT292580, MT292581, MT292582, MT293156, MT293157, MT293158, MT293159, MT293160, MT293161, MT293162, MT293163, MT293164, MT293165, MT293166, MT293167, MT293168, MT293169, MT293170, MT293171, MT293172, MT293173, MT293174, MT293175, MT293176, MT293177, MT293178, MT293179, MT293180, MT293181, MT293182, MT293183, MT293184, MT293185, MT293186, MT293187, MT293188, MT293189, MT293190, MT293191, MT293192, MT293193, MT293194, MT293195, MT293196, MT293197, MT293198, MT293199, MT293200, MT293201, MT293202, MT293203, MT293204, MT293205, MT293206, MT293207, MT293208, MT293209, MT293210, MT293211, MT293212, MT293213, MT293214, MT293215, MT293216, MT293217, MT293218, MT293219, MT293220, MT293221, MT293222, MT293223, MT293224, MT293225, MT295464, MT295465, MT276323, MT276324, MT276325, MT276326, MT276327, MT276328, MT276329, MT276330, MT276331, MT276597, MT276598, MT262896, MT262897, MT262898, MT262899, MT262900, MT262901, MT262902, MT262903, MT262904, MT262905, MT262906, MT262907, MT262908, MT262909, MT262910, MT262911, MT262912, MT262913, MT262914, MT262915, MT262916, MT262993, MT263074, MT263381, MT263382, MT263383, MT263384, MT263385, MT263386, MT263387, MT263388, MT263389, MT263390, MT263391, MT263392, MT263393, MT263394, MT263395, MT263396, MT263397, MT263398, MT263399, MT263400, MT263401, MT263402, MT263403, MT263404, MT263405, MT263406, MT263407, MT263408, MT263409, MT263410, MT263411, MT263412, MT263413, MT263414, MT263415, MT263416, MT263417, MT263418, MT263419, MT263420, MT263421, MT263422, MT263423, MT263424, MT263425, MT263426, MT263427, MT263428, MT263429, MT263430, MT263431, MT263432, MT263433, MT263434, MT263435, MT263436, MT263437, MT263438, MT263439, MT263440, MT263441, MT263442, MT263443, MT263444, MT263445, MT263446, MT263447, MT263448, MT263449, MT263450, MT263451, MT263452, MT263453, MT263454, MT263455, MT263456, MT263457, MT263458, MT263459, MT263460, MT263461, MT263462, MT263463, MT263464, MT263465, MT263466, MT263467, MT263468, MT263469, MT256917, MT256918, MT256924, MT258377, MT258378, MT258379, MT258380, MT258381, MT258382, MT258383, MT259226, MT259227, MT259228, MT259229, MT259230, MT259231, MT259235, MT259236, MT259237, MT259238, MT259239, MT259240, MT259241, MT259242, MT259243, MT259244, MT259245, MT259246, MT259247, MT259248, MT259249, MT259250, MT259251, MT259252, MT259253, MT259254, MT259255, MT259256, MT259257, MT259258, MT259259, MT259260, MT259261, MT259262, MT259263, MT259264, MT259265, MT259266, MT259267, MT259268, MT259269, MT259270, MT259271, MT259272, MT259273, MT259274, MT259275, MT259276, MT259277, MT259278, MT259279, MT259280, MT259281, MT259282, MT259283, MT259284, MT259285, MT259286, MT259287, LC534418, LC534419, MT251972, MT251973, MT251974, MT251975, MT251976, MT251977, MT251978, MT251979, MT251980, MT253696, MT253697, MT253698, MT253699, MT253700, MT253701, MT253702, MT253703, MT253704, MT253705, MT253706, MT253707, MT253708, MT253709, MT253710, MT233526, MT246449, MT246450, MT246451, MT246452, MT246453, MT246454, MT246455, MT246456, MT246457, MT246458, MT246459, MT246460, MT246461, MT246462, MT246463, MT246464, MT246465, MT246466, MT246467, MT246468, MT246469, MT246470, MT246471, MT246472, MT246473, MT246474, MT246475, MT246476, MT246477, MT246478, MT246479, MT246480, MT246481, MT246482, MT246483, MT246484, MT246485, MT246486, MT246487, MT246488, MT246489, MT246490, MT246667, MT240479, MT232869, MT232870, MT232871, MT232872, MT233519, MT233520, MT233521, MT233522, MT233523, MT226610, MT198651, MT198652, MT198653, MT192758, MT192759, MT192765, MT192772, MT192773, MT186676, MT186677, MT186678, MT186679, MT186680, MT186681, MT186682, MT187977, MT188339, MT188340, MT188341, CADDYA000000000, MT184907, MT184908, MT184909, MT184910, MT184911, MT184912, MT184913, MT163712, MT163714, MT163715, MT163716, MT163717, MT163718, MT163719, MT163720, MT163721, MT163737, MT163738, MT066156, MT121215, MT159705, MT159706, MT159707, MT159708, MT159709, MT159710, MT159711, MT159712, MT159713, MT159714, MT159715, MT159716, MT159717, MT159718, MT159719, MT159720, MT159721, MT159722, MT159778, MT161607, LC529905, MT012098, MT050493, MT152824, MT152900, MT135041, MT135042, MT135043, MT135044, MT126808, MT127113, MT127114, MT127115, MT127116, LC528232, LC528233, MT123290, MT123291, MT123292, MT123293, MT118835, MT111895, MT111896, MT106052, MT106053, MT106054, MT093571, MT093631, MT081059, MT081060, MT081061, MT081062, MT081063, MT081064, MT081065, MT081066, MT081067, MT081068, MT072667, MT072668, MT072688, MT066157, MT066158, MT066159, MT066175, MT066176, LC523807, LC523808, LC523809, MT042773, MT042774, MT042775, MT042776, MT042777, MT042778, MT044257, MT044258, MT049951, MT050414, MT050415, MT050416, MT050417, MT039873, MT039887, MT039888, MT039890, LC522350, MT027062, MT027063, MT027064, MT019529, MT019530, MT019531, MT019532, MT019533, MT020781, MT020880, MT020881, LR757995, LR757996, LR757997, LR757998, MT007544, MT008022, MT008023, MN996527, MN996528, MN996529, MN996530, MN996531, MN988668, MN988669, MN994467, MN994468, MN997409, MN988713, MN938384, MN938385, MN938386, MN938387, MN938388, MN938389, MN938390, MN975262, MN975263, MN975264, MN975265, MN975266, MN975267, MN975268, MN985325, MN970003, MN970004, or MN908947. 
     In certain embodiments, compounds described herein comprise or consist of an oligonucleotide comprising a region that is complementary to a SARS-CoV-2 RNA sequence, wherein the SARS-CoV2 RNA sequence is the B.1.1.7 variant identified in the United Kingdom. In certain embodiments, the RNA sequence of the B.1.1.7 variant is Genbank Accession No. MW487270. 
     In certain embodiments, compounds described herein comprise or consist of an oligonucleotide comprising a region that is complementary to a SARS-CoV-2 RNA sequence, wherein the SARS-CoV2 RNA sequence is the B.1.351 variant identified in South Africa. 
     In certain embodiments, compounds described herein comprise or consist of an oligonucleotide comprising a region that is complementary to a SARS-CoV-2 RNA sequence, wherein the SARS-CoV2 RNA sequence is the P.1 variant identified in Brazil. 
     In certain embodiments, compounds described herein comprise or consist of an oligonucleotide comprising a region that is complementary to a SARS-CoV-2 RNA sequence, wherein the SARS-CoV2 RNA sequence is the B.1.427/B.1.429 variant identified in California. 
     Hybridization 
     In some embodiments, hybridization occurs between a compound disclosed herein and a SARS-CoV-2 RNA. The most common mechanism of hybridization involves hydrogen bonding (e.g., Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding) between complementary nucleobases of the nucleic acid molecules. 
     Hybridization can occur under varying conditions. Hybridization conditions are sequence-dependent and are determined by the nature and composition of the nucleic acid molecules to be hybridized. 
     Methods of determining whether a sequence is specifically hybridizable to a target nucleic acid are well known in the art. In certain embodiments, the compounds provided herein are specifically hybridizable with a SARS-CoV-2 RNA. 
     Complementarity 
     An oligonucleotide is said to be complementary to another nucleic acid when the nucleobase sequence of such oligonucleotide or one or more regions thereof matches the nucleobase sequence of another oligonucleotide or nucleic acid or one or more regions thereof when the two nucleobase sequences are aligned in opposing directions. Nucleobase matches or complementary nucleobases, as described herein, are limited to the following pairs: adenine (A) and thymine (T), adenine (A) and uracil (U), cytosine (C) and guanine (G), and 5-methyl cytosine (mC) and guanine (G) unless otherwise specified. Complementary oligonucleotides and/or nucleic acids need not have nucleobase complementarity at each nucleoside and may include one or more nucleobase mismatches. An oligonucleotide is fully complementary or 100% complementary when such oligonucleotides have nucleobase matches at each nucleoside without any nucleobase mismatches. 
     In certain embodiments, compounds described herein comprise or consist of modified oligonucleotides. In certain embodiments, compounds described herein are antisense compounds. In certain embodiments, compounds comprise oligomeric compounds. Non-complementary nucleobases between a compound and a SARS-CoV-2 RNA may be tolerated provided that the compound remains able to specifically hybridize to a target nucleic acid. Moreover, a compound may hybridize over one or more segments of a SARS-CoV-2 RNA such that intervening or adjacent segments are not involved in the hybridization event (e.g., a loop structure, mismatch or hairpin structure). 
     In certain embodiments, the compounds provided herein, or a specified portion thereof, are, are at least, or are up to 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% complementary to a SARS-CoV-2 RNA, a target region, target segment, or specified portion thereof. In certain embodiments, the compounds provided herein, or a specified portion thereof, are 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 100%, or any number in between these ranges, complementary to a SARS-CoV-2 RNA, a target region, target segment, or specified portion thereof. Percent complementarity of a compound with a target nucleic acid can be determined using routine methods. 
     For example, a compound in which 18 of 20 nucleobases of the compound are complementary to a target region, and would therefore specifically hybridize, would represent 90 percent complementarity. In this example, the remaining non-complementary nucleobases may be clustered or interspersed with complementary nucleobases and need not be contiguous to each other or to complementary nucleobases. As such, a compound which is 18 nucleobases in length having four non-complementary nucleobases which are flanked by two regions of complete complementarity with the target nucleic acid would have 77.8% overall complementarity with the target nucleic acid. Percent complementarity of a compound with a region of a target nucleic acid can be determined routinely using BLAST programs (basic local alignment search tools) and PowerBLAST programs known in the art (Altschul et al.,  J. Mol. Biol.,  1990, 215, 403 410; Zhang and Madden,  Genome Res.,  1997, 7, 649 656). Percent homology, sequence identity or complementarity, can be determined by, for example, the Gap program (Wisconsin Sequence Analysis Package, Version 8 for Unix, Genetics Computer Group, University Research Park, Madison Wis.), using default settings, which uses the algorithm of Smith and Waterman (Adv. Appl. Math., 1981, 2, 482 489). 
     In certain embodiments, compounds described herein, or specified portions thereof, are fully complementary (i.e. 100% complementary) to a target nucleic acid, or specified portion thereof. For example, a compound may be fully complementary to a SARS-CoV-2 RNA, or a target region, or a target segment or target sequence thereof. As used herein, “fully complementary” means each nucleobase of a compound is complementary to the corresponding nucleobase of a target nucleic acid. For example, a 20 nucleobase compound is fully complementary to a target sequence that is 400 nucleobases long, so long as there is a corresponding 20 nucleobase portion of the target nucleic acid that is fully complementary to the compound. Fully complementary can also be used in reference to a specified portion of the first and/or the second nucleic acid. For example, a 20 nucleobase portion of a 30 nucleobase compound can be “fully complementary” to a target sequence that is 400 nucleobases long. The 20 nucleobase portion of the 30 nucleobase compound is fully complementary to the target sequence if the target sequence has a corresponding 20 nucleobase portion wherein each nucleobase is complementary to the 20 nucleobase portion of the compound. At the same time, the entire 30 nucleobase compound may or may not be fully complementary to the target sequence, depending on whether the remaining 10 nucleobases of the compound are also complementary to the target sequence. 
     In certain embodiments, compounds described herein comprise one or more mismatched nucleobases relative to the target nucleic acid. In certain such embodiments, antisense activity against the target is reduced by such mismatch, but activity against a non-target is reduced by a greater amount. Thus, in certain such embodiments selectivity of the compound is improved. In certain embodiments, the mismatch is specifically positioned within an oligonucleotide having a gapmer motif. In certain such embodiments, the mismatch is at position 1, 2, 3, 4, 5, 6, 7, or 8 from the 5′-end of the gap region. In certain such embodiments, the mismatch is at position 9, 8, 7, 6, 5, 4, 3, 2, 1 from the 3′-end of the gap region. In certain such embodiments, the mismatch is at position 1, 2, 3, or 4 from the 5′-end of the wing region. In certain such embodiments, the mismatch is at position 4, 3, 2, or 1 from the 3′-end of the wing region. In certain embodiments, the mismatch is specifically positioned within an oligonucleotide not having a gapmer motif. In certain such embodiments, the mismatch is at position 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 from the 5′-end of the oligonucleotide. In certain such embodiments, the mismatch is at position, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 from the 3′-end of the oligonucleotide. 
     The location of a non-complementary nucleobase may be at the 5′ end or 3′ end of the compound. Alternatively, the non-complementary nucleobase or nucleobases may be at an internal position of the compound. When two or more non-complementary nucleobases are present, they may be contiguous (i.e. linked) or non-contiguous. In one embodiment, a non-complementary nucleobase is located in the wing segment of a gapmer oligonucleotide. 
     In certain embodiments, compounds described herein that are, or are up to 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleobases in length comprise no more than 4, no more than 3, no more than 2, or no more than 1 non-complementary nucleobase(s) relative to a target nucleic acid, such as a SARS-CoV-2 RNA, or specified portion thereof. 
     In certain embodiments, compounds described herein that are, or are up to 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleobases in length comprise no more than 6, no more than 5, no more than 4, no more than 3, no more than 2, or no more than 1 non-complementary nucleobase(s) relative to a target nucleic acid, such as a SARS-CoV-2 RNA, or specified portion thereof. 
     In certain embodiments, compounds described herein also include those which are complementary to a portion of a target nucleic acid. As used herein, “portion” refers to a defined number of contiguous (i.e. linked) nucleobases within a region or segment of a target nucleic acid. A “portion” can also refer to a defined number of contiguous nucleobases of a compound. In certain embodiments, the compounds, are complementary to at least an 8 nucleobase portion of a target segment. In certain embodiments, the compounds are complementary to at least a 9 nucleobase portion of a target segment. In certain embodiments, the compounds are complementary to at least a 10 nucleobase portion of a target segment. In certain embodiments, the compounds are complementary to at least an 11 nucleobase portion of a target segment. In certain embodiments, the compounds are complementary to at least a 12 nucleobase portion of a target segment. In certain embodiments, the compounds are complementary to at least a 13 nucleobase portion of a target segment. In certain embodiments, the compounds are complementary to at least a 14 nucleobase portion of a target segment. In certain embodiments, the compounds are complementary to at least a 15 nucleobase portion of a target segment. In certain embodiments, the compounds are complementary to at least a 16 nucleobase portion of a target segment. Also contemplated are compounds that are complementary to at least a 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more nucleobase portion of a target segment, or a range defined by any two of these values. 
     Identity 
     The compounds provided herein may also have a defined percent identity to a particular nucleotide sequence, SEQ ID NO, or compound represented by a specific ION number, or portion thereof. In certain embodiments, compounds described herein are antisense compounds or oligomeric compounds. In certain embodiments, compounds described herein are modified oligonucleotides. As used herein, a compound is identical to the sequence disclosed herein if it has the same nucleobase pairing ability. For example, a RNA which contains uracil in place of thymidine in a disclosed DNA sequence would be considered identical to the DNA sequence since both uracil and thymidine pair with adenine. Shortened and lengthened versions of the compounds described herein as well as compounds having non-identical bases relative to the compounds provided herein also are contemplated. The non-identical bases may be adjacent to each other or dispersed throughout the compound. Percent identity of an compound is calculated according to the number of bases that have identical base pairing relative to the sequence to which it is being compared. 
     In certain embodiments, compounds described herein, or portions thereof, are, or are at least, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to one or more of the compounds or SEQ ID NOs, or a portion thereof, disclosed herein. In certain embodiments, compounds described herein are about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical, or any percentage between such values, to a particular nucleotide sequence, SEQ ID NO, or compound represented by a specific ION number, or portion thereof, in which the compounds comprise an oligonucleotide having one or more mismatched nucleobases. In certain such embodiments, the mismatch is at position 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 from the 5′-end of the oligonucleotide. In certain such embodiments, the mismatch is at position 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 from the 3′-end of the oligonucleotide. 
     In certain embodiments, compounds described herein comprise or consist of antisense compounds. In certain embodiments, a portion of the antisense compound is compared to an equal length portion of the target nucleic acid. In certain embodiments, an 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleobase portion is compared to an equal length portion of the target nucleic acid. 
     In certain embodiments, compounds described herein comprise or consist of oligonucleotides. In certain embodiments, a portion of the oligonucleotide is compared to an equal length portion of the target nucleic acid. In certain embodiments, an 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleobase portion is compared to an equal length portion of the target nucleic acid. 
     Certain Modified Compounds 
     In certain embodiments, compounds described herein comprise or consist of oligonucleotides consisting of linked nucleosides. Oligonucleotides may be unmodified oligonucleotides (RNA or DNA) or may be modified oligonucleotides. Modified oligonucleotides comprise at least one modification relative to unmodified RNA or DNA (i.e., comprise at least one modified nucleoside (comprising a modified sugar moiety and/or a modified nucleobase) and/or at least one modified internucleoside linkage). 
     A. Modified Nucleosides 
     Modified nucleosides comprise a modified sugar moiety or a modified nucleobase or both a modified sugar moiety and a modified nucleobase. 
     1. Modified Sugar Moieties 
     In certain embodiments, sugar moieties are non-bicyclic modified sugar moieties. In certain embodiments, modified sugar moieties are bicyclic or tricyclic sugar moieties. In certain embodiments, modified sugar moieties are sugar surrogates. Such sugar surrogates may comprise one or more substitutions corresponding to those of other types of modified sugar moieties. 
     In certain embodiments, modified sugar moieties are non-bicyclic modified sugar moieties comprising a furanosyl ring with one or more acyclic substituent, including but not limited to substituents at the 2′, 4′, and/or 5′ positions. In certain embodiments one or more acyclic substituent of non-bicyclic modified sugar moieties is branched. Examples of 2′-substituent groups suitable for non-bicyclic modified sugar moieties include but are not limited to: 2′-F, 2′-OCH 3  (“OMe” or “O-methyl”), and 2′-O(CH 2 ) 2 OCH 3  (“MOE”). In certain embodiments, 2′-substituent groups are selected from among: halo, allyl, amino, azido, SH, CN, OCN, CF 3 , OCF 3 , O—C 1 -C 10  alkoxy, O—C 1 -C 10  substituted alkoxy, O—C 1 -C 10  alkyl, O—C 1 -C 10  substituted alkyl, S-alkyl, N(R m )-alkyl, O-alkenyl, S-alkenyl, N(R m )-alkenyl, O-alkynyl, S-alkynyl, N(R m )-alkynyl, O-alkylenyl-O-alkyl, alkynyl, alkaryl, aralkyl, O-alkaryl, O-aralkyl, O(CH 2 ) 2 SCH 3 , O(CH 2 ) 2 ON(R m )(R m ) or OCH 2 C(═O)—N(R m )(R n ), where each R m  and R n  is, independently, H, an amino protecting group, or substituted or unsubstituted C 1 -C 10 alkyl, and the 2′-substituent groups described in Cook et al., U.S. Pat. No. 6,531,584; Cook et al., U.S. Pat. No. 5,859,221; and Cook et al., U.S. Pat. No. 6,005,087. Certain embodiments of these 2′-substituent groups can be further substituted with one or more substituent groups independently selected from among: hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro (NO 2 ), thiol, thioalkoxy, thioalkyl, halogen, alkyl, aryl, alkenyl and alkynyl. Examples of 4′-substituent groups suitable for linearly non-bicyclic modified sugar moieties include but are not limited to alkoxy (e.g., methoxy), alkyl, and those described in Manoharan et al., WO 2015/106128. Examples of 5′-substituent groups suitable for non-bicyclic modified sugar moieties include but are not limited to: 5′-methyl (R or S), 5′-vinyl, and 5′-methoxy. In certain embodiments, non-bicyclic modified sugars comprise more than one non-bridging sugar substituent, for example, 2′-F-5′-methyl sugar moieties and the modified sugar moieties and modified nucleosides described in Migawa et al., US2010/190837 and Rajeev et al., US2013/0203836. 
     In certain embodiments, a 2′-substituted nucleoside or 2′-non-bicyclic modified nucleoside comprises a sugar moiety comprising a linear 2′-substituent group selected from: F, NH 2 , N 3 , OCF 3 , OCH 3 , O(CH 2 ) 3 NH 2 , CH 2 CH═CH 2 , OCH 2 CH═CH 2 , OCH 2 CH 2 OCH 3 , O(CH 2 ) 2 SCH 3 , O(CH 2 ) 2 ON(R m )(R n ), O(CH 2 ) 2 O(CH 2 ) 2 N(CH 3 ) 2 , and N-substituted acetamide (OCH 2 C(═O)—N(R m )(R n )), where each R m  and R n  is, independently, H, an amino protecting group, or substituted or unsubstituted C 1 -C 10  alkyl. 
     In certain embodiments, a 2′-substituted nucleoside or 2′-non-bicyclic modified nucleoside comprises a sugar moiety comprising a linear 2′-substituent group selected from: F, OCF 3 , OCH 3 , OCH 2 CH 2 OCH 3 , O(CH 2 ) 2 SCH 3 , O(CH 2 ) 2 ON(CH 3 ) 2 , O(CH 2 ) 2 O(CH 2 ) 2 N(CH 3 ) 2 , and OCH 2 C(═O)—N(H)CH 3  (“NMA”). 
     In certain embodiments, a 2′-substituted nucleoside or 2′-non-bicyclic modified nucleoside comprises a sugar moiety comprising a linear 2′-substituent group selected from: F, OCH 3 , and OCH 2 CH 2 OCH 3 . 
     Nucleosides comprising modified sugar moieties, such as non-bicyclic modified sugar moieties, are referred to by the position(s) of the substitution(s) on the sugar moiety of the nucleoside. For example, nucleosides comprising 2′-substituted or 2-modified sugar moieties are referred to as 2′-substituted nucleosides or 2-modified nucleosides. 
     Certain modified sugar moieties comprise a bridging sugar substituent that forms a second ring resulting in a bicyclic sugar moiety. In certain such embodiments, the bicyclic sugar moiety comprises a bridge between the 4′ and the 2′ furanose ring atoms. Examples of such 4′ to 2′ bridging sugar substituents include but are not limited to: 4′-CH 2 -2′, 4′-(CH 2 ) 2 -2′, 4′-(CH 2 ) 3 -2′, 4′-CH 2 —O-2′ (“LNA”), 4′-CH 2 —S-2′, 4′-(CH 2 ) 2 —O-2′ (“ENA”), 4′-CH(CH 3 )—O-2′ (referred to as “constrained ethyl” or “cEt” when in the S configuration), 4′-CH 2 —O—CH 2 -2′, 4′-CH 2 —N(R)-2′, 4′-CH(CH 2 OCH 3 )—O-2′ (“constrained MOE” or “cMOE”) and analogs thereof (see, e.g., Seth et al., U.S. Pat. No. 7,399,845, Bhat et al., U.S. Pat. No. 7,569,686, Swayze et al., U.S. Pat. No. 7,741,457, and Swayze et al., U.S. Pat. No. 8,022,193), 4′-C(CH 3 )(CH 3 )—O-2′ and analogs thereof (see, e.g., Seth et al., U.S. Pat. No. 8,278,283), 4′-CH 2 —N(OCH 3 )-2′ and analogs thereof (see, e.g., Prakash et al., U.S. Pat. No. 8,278,425), 4′-CH 2 —O—N(CH 3 )-2′ (see, e.g., Allerson et al., U.S. Pat. No. 7,696,345 and Allerson et al., U.S. Pat. No. 8,124,745), 4′-CH 2 —C(H)(CH 3 )-2′ (see, e.g., Zhou, et al.,  J. Org. Chem.,  2009, 74, 118-134), 4′-CH 2 —C(═CH 2 )-2′ and analogs thereof (see e.g., Seth et al., U.S. Pat. No. 8,278,426), 4′-C(R a R b )—N(R)—O-2′, 4′-C(R a R b )—O—N(R)-2′, 4′-CH 2 —O—N(R)-2′, and 4′-CH 2 —N(R)—O-2′, wherein each R, R a , and R b  is, independently, H, a protecting group, or C 1 -C 12  alkyl (see, e.g. Imanishi et al., U.S. Pat. No. 7,427,672). 
     In certain embodiments, such 4′ to 2′ bridges independently comprise from 1 to 4 linked groups independently selected from: —[C(R a )(R b )] n —, —[C(R a )(R b )] n —O—, —C(R a )═C(R b )—, —C(R a )═N—, —C(═NR)—, —C(═O)—, —C(═S)—, —O—, —Si(R a ) 2 —, —S(═O) x —, and —N(R a )—; 
     wherein: 
     x is 0, 1, or 2; 
     n is 1, 2, 3, or 4; 
     each R a  and R b  is, independently, H, a protecting group, hydroxyl, C 1 -C 12  alkyl, substituted C 1 -C 12  alkyl, C 2 -C 12  alkenyl, substituted C 2 -C 12  alkenyl, C 2 -C 12  alkynyl, substituted C 2 -C 12  alkynyl, C 5 -C 20  aryl, substituted C 5 -C 20  aryl, heterocycle radical, substituted heterocycle radical, heteroaryl, substituted heteroaryl, C 5 -C 7  alicyclic radical, substituted C 5 -C 7  alicyclic radical, halogen, OJ 1 , NJ 1 J 2 , SJ 1 , N 3 , COOJ 1 , acyl (C(═O)—H), substituted acyl, CN, sulfonyl (S(═O) 2 -J 1 ), or sulfoxyl (S(═O)-J 1 ); and each J 1  and J 2  is, independently, H, C 1 -C 12  alkyl, substituted C 1 -C 12  alkyl, C 2 -C 12  alkenyl, substituted C 2 -C 12  alkenyl, C 2 -C 12  alkynyl, substituted C 2 -C 12  alkynyl, C 5 -C 20  aryl, substituted C 5 -C 20  aryl, acyl (C(═O)—H), substituted acyl, a heterocycle radical, a substituted heterocycle radical, C 1 -C 12  aminoalkyl, substituted C 1 -C 12  aminoalkyl, or a protecting group. 
     Additional bicyclic sugar moieties are known in the art, see, for example: Freier et al.,  Nucleic Acids Research,  1997, 25(22), 4429-4443, Albaek et al.,  J. Org. Chem.,  2006, 71, 7731-7740, Singh et al.,  Chem. Commun.,  1998, 4, 455-456; Koshkin et al.,  Tetrahedron,  1998, 54, 3607-3630; Wahlestedt et al.,  Proc. Natl. Acad. Sci. U.S.A.,  2000, 97, 5633-5638; Kumar et al.,  Bioorg. Med. Chem. Lett.,  1998, 8, 2219-2222; Singh et al.,  J. Org. Chem.,  1998, 63, 10035-10039; Srivastava et al.,  J. Am. Chem. Soc.,  2007, 129, 8362-8379; Elayadi et al.,  Curr. Opinion Invens. Drugs.  2001, 2, 558-561; Braasch et al.,  Chem. Biol.,  2001, 8, 1-7; Orum et al.,  Curr. Opinion Mol. Ther.,  2001, 3, 239-243; Wengel et al., U.S. Pat. No. 7,053,207, Imanishi et al., U.S. Pat. No. 6,268,490, Imanishi et al. U.S. Pat. No. 6,770,748, Imanishi et al., U.S. RE44,779; Wengel et al., U.S. Pat. No. 6,794,499, Wengel et al., U.S. Pat. No. 6,670,461; Wengel et al., U.S. Pat. No. 7,034,133, Wengel et al., U.S. Pat. No. 8,080,644; Wengel et al., U.S. Pat. No. 8,034,909; Wengel et al., U.S. Pat. No. 8,153,365; Wengel et al., U.S. Pat. No. 7,572,582; and Ramasamy et al., U.S. Pat. No. 6,525,191, Torsten et al., WO 2004/106356, Wengel et al., WO 1999/014226; Seth et al., WO 2007/134181; Seth et al., U.S. Pat. No. 7,547,684; Seth et al., U.S. Pat. No. 7,666,854; Seth et al., U.S. Pat. No. 8,088,746; Seth et al., U.S. Pat. No. 7,750,131; Seth et al., U.S. Pat. No. 8,030,467; Seth et al., U.S. Pat. No. 8,268,980; Seth et al., U.S. Pat. No. 8,546,556; Seth et al., U.S. Pat. No. 8,530,640; Migawa et al., U.S. Pat. No. 9,012,421; Seth et al., U.S. Pat. No. 8,501,805; Allerson et al., US2008/0039618; and Migawa et al., US2015/0191727. 
     In certain embodiments, bicyclic sugar moieties and nucleosides incorporating such bicyclic sugar moieties are further defined by isomeric configuration. For example, an LNA nucleoside (described herein) may be in the α-L configuration or in the β-D configuration. 
     
       
         
         
             
             
         
       
     
     α-L-methyleneoxy (4′-CH 2 —O—2′) or α-L-LNA bicyclic nucleosides have been incorporated into oligonucleotides that showed antisense activity (Frieden et al.,  Nucleic Acids Research.  2003, 21, 6365-6372). Herein, general descriptions of bicyclic nucleosides include both isomeric configurations. When the positions of specific bicyclic nucleosides (e.g., LNA or cEt) are identified in exemplified embodiments herein, they are in the β-D configuration, unless otherwise specified. 
     In certain embodiments, modified sugar moieties comprise one or more non-bridging sugar substituent and one or more bridging sugar substituent (e.g., 5′-substituted and 4′-2′ bridged sugars). 
     In certain embodiments, modified sugar moieties are sugar surrogates. In certain such embodiments, the oxygen atom of the sugar moiety is replaced, e.g., with a sulfur, carbon or nitrogen atom. In certain such embodiments, such modified sugar moieties also comprise bridging and/or non-bridging substituents as described herein. For example, certain sugar surrogates comprise a 4′-sulfur atom and a substitution at the 2′-position (see, e.g., Bhat et al., U.S. Pat. No. 7,875,733 and Bhat et al., U.S. Pat. No. 7,939,677) and/or the 5′ position. 
     In certain embodiments, sugar surrogates comprise rings having other than 5 atoms. For example, in certain embodiments, a sugar surrogate comprises a six-membered tetrahydropyran (“THP”). Such tetrahydropyrans may be further modified or substituted. Nucleosides comprising such modified tetrahydropyrans include but are not limited to hexitol nucleic acid (“HNA”), anitol nucleic acid (“ANA”), manitol nucleic acid (“MNA”) (see e.g., Leumann, C J.  Boorg . &amp;  Med. Chem.  2002, 10, 841-854), fluoro HNA: 
     
       
         
         
             
             
         
       
     
     (“F-HNA”, see e.g., Swayze et al., U.S. Pat. No. 8,088,904; Swayze et al., U.S. Pat. No. 8,440,803; and Swayze et al., U.S. Pat. No. 9,005,906, F-HNA can also be referred to as a F-THP or 3′-fluoro tetrahydropyran), and nucleosides comprising additional modified THP compounds having the formula: 
     
       
         
         
             
             
         
       
     
     wherein, independently, for each of said modified THP nucleoside: 
     Bx is a nucleobase moiety; 
     T 3  and T 4  are each, independently, an internucleoside linking group linking the modified THP nucleoside to the remainder of an oligonucleotide or one of T 3  and T 4  is an internucleoside linking group linking the modified THP nucleoside to the remainder of an oligonucleotide and the other of T 3  and T 4  is H, a hydroxyl protecting group, a linked conjugate group, or a 5′ or 3′-terminal group; q 1 , q 2 , q 3 , q 4 , q 5 , q 6  and q 7  are each, independently, H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, C 2 -C 6  alkenyl, substituted C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, or substituted C 2 -C 6  alkynyl; and each of R 1  and R 2  is independently selected from among: hydrogen, halogen, substituted or unsubstituted alkoxy, NJ 1 J 2 , SJ 1 , N 3 , OC(═X)J 1 , OC(═X)NJ 1 J 2 , NJ 3 C(═X)NJ 1 J 2 , and CN, wherein X is O, S or NJ 1 , and each J 1 , J 2 , and J 3  is, independently, H or C 1 -C 6  alkyl. 
     In certain embodiments, modified THP nucleosides are provided wherein q 1 , q 2 , q 3 , q 4 , q 5 , q 6  and q 7  are each H. In certain embodiments, at least one of q 1 , q 2 , q 3 , q 4 , q 5 , q 6  and q 7  is other than H. In certain embodiments, at least one of q 1 , q 2 , q 3 , q 4 , q 5 , q 6  and q 7  is methyl. In certain embodiments, modified THP nucleosides are provided wherein one of R 1  and R 2  is F. In certain embodiments, R 1  is F and R 2  is H, in certain embodiments, R 1  is methoxy and R 2  is H, and in certain embodiments, R 1  is methoxyethoxy and R 2  is H. 
     In certain embodiments, sugar surrogates comprise rings having more than 5 atoms and more than one heteroatom. For example, nucleosides comprising morpholino sugar moieties and their use in oligonucleotides have been reported (see, e.g., Braasch et al., Biochemistry, 2002, 41, 4503-4510 and Summerton et al., U.S. Pat. No. 5,698,685; Summerton et al., U.S. Pat. No. 5,166,315; Summerton et al., U.S. Pat. No. 5,185,444; and Summerton et al., U.S. Pat. No. 5,034,506). As used here, the term “morpholino” means a sugar surrogate having the following structure: 
     
       
         
         
             
             
         
       
     
     In certain embodiments, morpholinos may be modified, for example by adding or altering various substituent groups from the above morpholino structure. Such sugar surrogates are referred to herein as “modified morpholinos.” 
     In certain embodiments, sugar surrogates comprise acyclic moieties. Examples of nucleosides and oligonucleotides comprising such acyclic sugar surrogates include but are not limited to: peptide nucleic acid (“PNA”), acyclic butyl nucleic acid (see, e.g., Kumar et al.,  Org. Biomol. Chem.,  2013, 11, 5853-5865), and nucleosides and oligonucleotides described in Manoharan et al., US2013/130378. 
     Many other bicyclic and tricyclic sugar and sugar surrogate ring systems are known in the art that can be used in modified nucleosides. 
     2. Modified Nucleobases 
     Nucleobase (or base) modifications or substitutions are structurally distinguishable from, yet functionally interchangeable with, naturally occurring or synthetic unmodified nucleobases. Both natural and modified nucleobases are capable of participating in hydrogen bonding. Such nucleobase modifications can impart nuclease stability, binding affinity or some other beneficial biological property to antisense compounds. 
     In certain embodiments, compounds described herein comprise modified oligonucleotides. In certain embodiments, modified oligonucleotides comprise one or more nucleoside comprising an unmodified nucleobase. In certain embodiments, modified oligonucleotides comprise one or more nucleoside comprising a modified nucleobase. In certain embodiments, modified oligonucleotides comprise one or more nucleoside that does not comprise a nucleobase, referred to as an abasic nucleoside. 
     In certain embodiments, modified nucleobases are selected from: 5-substituted pyrimidines, 6-azapyrimi-dines, alkyl or alkynyl substituted pyrimidines, alkyl substituted purines, and N-2, N-6 and O-6 substituted purines. In certain embodiments, modified nucleobases are selected from: 2-aminopropyladenine, 5-hydroxymethyl cytosine, 5-methylcytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-N-methylguanine, 6-N-methyladenine, 2-propyladenine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-propynyl (C≡C—CH3) uracil, 5-propynylcytosine, 6-azouracil, 6-azocytosine, 6-azothymine, 5-ribosyluracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl, 8-aza and other 8-substituted purines, 5-halo, particularly 5-bromo, 5-trifluoromethyl, 5-halouracil, and 5-halocytosine, 7-methylguanine, 7-methyladenine, 2-F-adenine, 2-aminoadenine, 7-deazaguanine, 7-deazaadenine, 3-deazaguanine, 3-deazaadenine, 6-N-benzoyladenine, 2-N-isobutyrylguanine, 4-N-benzoylcytosine, 4-N-benzoyluracil, 5-methyl 4-N-benzoylcytosine, 5-methyl 4-N-benzoyluracil, universal bases, hydrophobic bases, promiscuous bases, size-expanded bases, and fluorinated bases. Further modified nucleobases include tricyclic pyrimidines, such as 1,3-diazaphenoxazine-2-one, 1,3-diazaphenothiazine-2-one and 9-(2-aminoethoxy)-1,3-diazaphenoxazine-2-one (G-clamp). Modified nucleobases may also include those in which the purine or pyrimidine base is replaced with other heterocycles, for example 7-deaza-adenine, 7-deazaguanosine, 2-aminopyridine and 2-pyridone. Further nucleobases include those disclosed in Merigan et al., U.S. Pat. No. 3,687,808, those disclosed in The Concise Encyclopedia Of Polymer Science And Engineering, Kroschwitz, J. I., Ed., John Wiley &amp; Sons, 1990, 858-859; Englisch et al., Angewandte Chemie, International Edition, 1991, 30,613; Sanghvi, Y. S., Chapter 15, Antisense Research and Applications, Crooke, S. T. and Lebleu, B., Eds., CRC Press, 1993, 273-288; and those disclosed in Chapters 6 and 15, Antisense Drug Technology, Crooke S. T., Ed., CRC Press, 2008, 163-166 and 442-443. 
     Publications that teach the preparation of certain of the above noted modified nucleobases as well as other modified nucleobases include without limitation, Manoharan et al., US2003/0158403, Manoharan et al., US2003/0175906; Dinh et al., U.S. Pat. No. 4,845,205; Spielvogel et al., U.S. Pat. No. 5,130,302; Rogers et al., U.S. Pat. No. 5,134,066; Bischofberger et al., U.S. Pat. No. 5,175,273; Urdea et al., U.S. Pat. No. 5,367,066; Benner et al., U.S. Pat. No. 5,432,272; Matteucci et al., U.S. Pat. No. 5,434,257; Gmeiner et al., U.S. Pat. No. 5,457,187; Cook et al., U.S. Pat. No. 5,459,255; Froehler et al., U.S. Pat. No. 5,484,908; Matteucci et al., U.S. Pat. No. 5,502,177; Hawkins et al., U.S. Pat. No. 5,525,711; Haralambidis et al., U.S. Pat. No. 5,552,540; Cook et al., U.S. Pat. No. 5,587,469; Froehler et al., U.S. Pat. No. 5,594,121; Switzer et al., U.S. Pat. No. 5,596,091; Cook et al., U.S. Pat. No. 5,614,617; Froehler et al., U.S. Pat. No. 5,645,985; Cook et al., U.S. Pat. No. 5,681,941; Cook et al., U.S. Pat. No. 5,811,534; Cook et al., U.S. Pat. No. 5,750,692; Cook et al., U.S. Pat. No. 5,948,903; Cook et al., U.S. Pat. No. 5,587,470; Cook et al., U.S. Pat. No. 5,457,191; Matteucci et al., U.S. Pat. No. 5,763,588; Froehler et al., U.S. Pat. No. 5,830,653; Cook et al., U.S. Pat. No. 5,808,027; Cook et al., U.S. Pat. No. 6,166,199; and Matteucci et al., U.S. Pat. No. 6,005,096. 
     In certain embodiments, compounds targeted to a SARS-CoV-2 RNA comprise one or more modified nucleobases. In certain embodiments, the modified nucleobase is 5-methylcytosine. In certain embodiments, each cytosine is a 5-methylcytosine. 
     3. Modified Internucleoside Linkages 
     The naturally occurring internucleoside linkage of RNA and DNA is a 3′ to 5′ phosphodiester linkage In certain embodiments, compounds described herein having one or more modified, i.e. non-naturally occurring, internucleoside linkages are often selected over compounds having naturally occurring internucleoside linkages because of desirable properties such as, for example, enhanced cellular uptake, enhanced affinity for target nucleic acids, and increased stability in the presence of nucleases. 
     Representative internucleoside linkages having a chiral center include but are not limited to alkylphosphonates and phosphorothioates. Modified oligonucleotides comprising internucleoside linkages having a chiral center can be prepared as populations of modified oligonucleotides comprising stereorandom internucleoside linkages, or as populations of modified oligonucleotides comprising phosphorothioate linkages in particular stereochemical configurations. In certain embodiments, populations of modified oligonucleotides comprise phosphorothioate internucleoside linkages wherein all of the phosphorothioate internucleoside linkages are stereorandom. Such modified oligonucleotides can be generated using synthetic methods that result in random selection of the stereochemical configuration of each phosphorothioate linkage. Nonetheless, as is well understood by those of skill in the art, each individual phosphorothioate of each individual oligonucleotide molecule has a defined stereoconfiguration. In certain embodiments, populations of modified oligonucleotides are enriched for modified oligonucleotides comprising one or more particular phosphorothioate internucleoside linkages in a particular, independently selected stereochemical configuration. In certain embodiments, the particular configuration of the particular phosphorothioate linkage is present in at least 65% of the molecules in the population. In certain embodiments, the particular configuration of the particular phosphorothioate linkage is present in at least 70% of the molecules in the population. In certain embodiments, the particular configuration of the particular phosphorothioate linkage is present in at least 80% of the molecules in the population. In certain embodiments, the particular configuration of the particular phosphorothioate linkage is present in at least 90% of the molecules in the population. In certain embodiments, the particular configuration of the particular phosphorothioate linkage is present in at least 99% of the molecules in the population. Such chirally enriched populations of modified oligonucleotides can be generated using synthetic methods known in the art, e.g., methods described in Oka et al.,  JACS  125, 8307 (2003), Wan et al.  Nuc. Acid. Res.  42, 13456 (2014), and WO 2017/015555. In certain embodiments, a population of modified oligonucleotides is enriched for modified oligonucleotides having at least one indicated phosphorothioate in the (Sp) configuration. In certain embodiments, a population of modified oligonucleotides is enriched for modified oligonucleotides having at least one phosphorothioate in the (Rp) configuration. In certain embodiments, modified oligonucleotides comprising (Rp) and/or (Sp) phosphorothioates comprise one or more of the following formulas, respectively, wherein “B” indicates a nucleobase: 
     
       
         
         
             
             
         
       
     
     Unless otherwise indicated, chiral internucleoside linkages of modified oligonucleotides described herein can be stereorandom or in a particular stereochemical configuration. 
     In certain embodiments, compounds targeted to an SARS-CoV-2 RNA comprise one or more modified internucleoside linkages. In certain embodiments, the modified internucleoside linkages are phosphorothioate linkages. In certain embodiments, each internucleoside linkage of an antisense compound is a phosphorothioate internucleoside linkage. 
     In certain embodiments, compounds described herein comprise oligonucleotides. Oligonucleotides having modified internucleoside linkages include internucleoside linkages that retain a phosphorus atom as well as internucleoside linkages that do not have a phosphorus atom. Representative phosphorus containing internucleoside linkages include, but are not limited to, phosphodiesters, phosphotriesters, methylphosphonates, phosphoramidate, and phosphorothioates. Methods of preparation of phosphorous-containing and non-phosphorous-containing linkages are well known. 
     In certain embodiments, nucleosides of modified oligonucleotides may be linked together using any internucleoside linkage. The two main classes of internucleoside linking groups are defined by the presence or absence of a phosphorus atom. Representative phosphorus-containing internucleoside linkages include but are not limited to phosphates, which contain a phosphodiester bond (“P═O”) (also referred to as unmodified or naturally occurring linkages), phosphotriesters, methylphosphonates, phosphoramidates, and phosphorothioates (“P═S”), and phosphorodithioates (“HS-P═S”). Representative non-phosphorus containing internucleoside linking groups include but are not limited to methylenemethylimino (—CH2-N(CH3)-O—CH2-), thiodiester, thionocarbamate (—O—C(═O)(NH)—S—); siloxane (—O—SiH2-O—); and N,N′-dimethylhydrazine (—CH2-N(CH3)-N(CH3)-). Modified internucleoside linkages, compared to naturally occurring phosphate linkages, can be used to alter, typically increase, nuclease resistance of the oligonucleotide. In certain embodiments, internucleoside linkages having a chiral atom can be prepared as a racemic mixture, or as separate enantiomers. Representative chiral internucleoside linkages include but are not limited to alkylphosphonates and phosphorothioates. Methods of preparation of phosphorous-containing and non-phosphorous-containing internucleoside linkages are well known to those skilled in the art. 
     Neutral internucleoside linkages include, without limitation, phosphotriesters, methylphosphonates, MMI (3′-CH2-N(CH3)-O-5′), amide-3 (3′-CH2-C(═O)—N(H)-5′), amide-4 (3′-CH2-N(H)—C(═O)-5′), formacetal (3′-O—CH2-O-5′), methoxypropyl, and thioformacetal (3′-S—CH2-O-5′). Further neutral internucleoside linkages include nonionic linkages comprising siloxane (dialkylsiloxane), carboxylate ester, carboxamide, sulfide, sulfonate ester and amides (See for example: Carbohydrate Modifications in Antisense Research; Y. S. Sanghvi and P. D. Cook, Eds., ACS Symposium Series 580; Chapters 3 and 4, 40-65). Further neutral internucleoside linkages include nonionic linkages comprising mixed N, O, S and CH2 component parts. 
     In certain embodiments, oligonucleotides comprise modified internucleoside linkages arranged along the oligonucleotide or region thereof in a defined pattern or modified internucleoside linkage motif. In certain embodiments, internucleoside linkages are arranged in a gapped motif. In such embodiments, the internucleoside linkages in each of two wing regions are different from the internucleoside linkages in the gap region. In certain embodiments the internucleoside linkages in the wings are phosphodiester and the internucleoside linkages in the gap are phosphorothioate. The nucleoside motif is independently selected, so such oligonucleotides having a gapped internucleoside linkage motif may or may not have a gapped nucleoside motif and if it does have a gapped nucleoside motif, the wing and gap lengths may or may not be the same. 
     In certain embodiments, oligonucleotides comprise a region having an alternating internucleoside linkage motif. In certain embodiments, oligonucleotides comprise a region of uniformly modified internucleoside linkages. In certain such embodiments, the oligonucleotide comprises a region that is uniformly linked by phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide is uniformly linked by phosphorothioate. In certain embodiments, each internucleoside linkage of the oligonucleotide is selected from phosphodiester and phosphorothioate. In certain embodiments, each internucleoside linkage of the oligonucleotide is selected from phosphodiester and phosphorothioate and at least one internucleoside linkage is phosphorothioate. 
     In certain embodiments, the oligonucleotide comprises at least 6 phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide comprises at least 8 phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide comprises at least 10 phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide comprises at least one block of at least 6 consecutive phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide comprises at least one block of at least 8 consecutive phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide comprises at least one block of at least 10 consecutive phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide comprises at least block of at least one 12 consecutive phosphorothioate internucleoside linkages. In certain such embodiments, at least one such block is located at the 3′ end of the oligonucleotide. In certain such embodiments, at least one such block is located within 3 nucleosides of the 3′ end of the oligonucleotide. 
     In certain embodiments, oligonucleotides comprise one or more methylphosponate linkages. In certain embodiments, oligonucleotides having a gapmer nucleoside motif comprise a linkage motif comprising all phosphorothioate linkages except for one or two methylphosponate linkages. In certain embodiments, one methylphosponate linkage is in the central gap of an oligonucleotide having a gapmer nucleoside motif. 
     In certain embodiments, it is desirable to arrange the number of phosphorothioate internucleoside linkages and phosphodiester internucleoside linkages to maintain nuclease resistance. In certain embodiments, it is desirable to arrange the number and position of phosphorothioate internucleoside linkages and the number and position of phosphodiester internucleoside linkages to maintain nuclease resistance. In certain embodiments, the number of phosphorothioate internucleoside linkages may be decreased and the number of phosphodiester internucleoside linkages may be increased. In certain embodiments, the number of phosphorothioate internucleoside linkages may be decreased and the number of phosphodiester internucleoside linkages may be increased while still maintaining nuclease resistance. In certain embodiments it is desirable to decrease the number of phosphorothioate internucleoside linkages while retaining nuclease resistance. In certain embodiments it is desirable to increase the number of phosphodiester internucleoside linkages while retaining nuclease resistance. 
     Certain Motifs 
     In certain embodiments, compounds described herein comprise oligonucleotides. Oligonucleotides can have a motif, e.g. a pattern of unmodified and/or modified sugar moieties, nucleobases, and/or internucleoside linkages. In certain embodiments, modified oligonucleotides comprise one or more modified nucleoside comprising a modified sugar. In certain embodiments, modified oligonucleotides comprise one or more modified nucleosides comprising a modified nucleobase. In certain embodiments, modified oligonucleotides comprise one or more modified internucleoside linkage. In such embodiments, the modified, unmodified, and differently modified sugar moieties, nucleobases, and/or internucleoside linkages of a modified oligonucleotide define a pattern or motif. In certain embodiments, the patterns of sugar moieties, nucleobases, and internucleoside linkages are each independent of one another. Thus, a modified oligonucleotide may be described by its sugar motif, nucleobase motif and/or internucleoside linkage motif (as used herein, nucleobase motif describes the modifications to the nucleobases independent of the sequence of nucleobases). 
     a. Certain Sugar Motifs 
     In certain embodiments, compounds described herein comprise oligonucleotides. In certain embodiments, oligonucleotides comprise one or more type of modified sugar and/or unmodified sugar moiety arranged along the oligonucleotide or region thereof in a defined pattern or sugar motif. In certain instances, such sugar motifs include but are not limited to any of the sugar modifications discussed herein. 
     In certain embodiments, modified oligonucleotides comprise or consist of a region having a gapmer motif, which comprises two external regions or “wings” and a central or internal region or “gap.” The three regions of a gapmer motif (the 5′-wing, the gap, and the 3′-wing) form a contiguous sequence of nucleosides wherein at least some of the sugar moieties of the nucleosides of each of the wings differ from at least some of the sugar moieties of the nucleosides of the gap. Specifically, at least the sugar moieties of the nucleosides of each wing that are closest to the gap (the 3′-most nucleoside of the 5′-wing and the 5′-most nucleoside of the 3′-wing) differ from the sugar moiety of the neighboring gap nucleosides, thus defining the boundary between the wings and the gap (i.e., the wing/gap junction). In certain embodiments, the sugar moieties within the gap are the same as one another. In certain embodiments, the gap includes one or more nucleoside having a sugar moiety that differs from the sugar moiety of one or more other nucleosides of the gap. In certain embodiments, the sugar motifs of the two wings are the same as one another (symmetric gapmer). In certain embodiments, the sugar motif of the 5′-wing differs from the sugar motif of the 3′-wing (asymmetric gapmer). 
     In certain embodiments, the wings of a gapmer comprise 1-5 nucleosides. In certain embodiments, the wings of a gapmer comprise 2-5 nucleosides. In certain embodiments, the wings of a gapmer comprise 3-5 nucleosides. In certain embodiments, the nucleosides of a gapmer are all modified nucleosides. 
     In certain embodiments, the gap of a gapmer comprises 7-12 nucleosides. In certain embodiments, the gap of a gapmer comprises 7-10 nucleosides. In certain embodiments, the gap of a gapmer comprises 8-10 nucleosides. In certain embodiments, the gap of a gapmer comprises 10 nucleosides. In certain embodiment, each nucleoside of the gap of a gapmer is an unmodified 2′-deoxy nucleoside. 
     In certain embodiments, the gapmer is a deoxy gapmer. In such embodiments, the nucleosides on the gap side of each wing/gap junction are unmodified 2′-deoxy nucleosides and the nucleosides on the wing sides of each wing/gap junction are modified nucleosides. In certain such embodiments, each nucleoside of the gap is an unmodified 2′-deoxy nucleoside. In certain such embodiments, each nucleoside of each wing is a modified nucleoside. 
     In certain embodiments, a modified oligonucleotide has a fully modified sugar motif wherein each nucleoside of the modified oligonucleotide comprises a modified sugar moiety. In certain embodiments, modified oligonucleotides comprise or consist of a region having a fully modified sugar motif wherein each nucleoside of the region comprises a modified sugar moiety. In certain embodiments, modified oligonucleotides comprise or consist of a region having a fully modified sugar motif, wherein each nucleoside within the fully modified region comprises the same modified sugar moiety, referred to herein as a uniformly modified sugar motif. In certain embodiments, a fully modified oligonucleotide is a uniformly modified oligonucleotide. In certain embodiments, each nucleoside of a uniformly modified comprises the same 2′-modification. 
     In certain embodiments, a modified oligonucleotide can comprise a sugar motif described in Swayze et al., US2010/0197762; Freier et al., US2014/0107330; Freier et al., US2015/0184153; and Seth et al., US2015/0267195, each of which is incorporated by reference in its entirety herein. 
     Certain embodiments provided herein are directed to modified oligomeric compounds useful for inhibiting target nucleic acid expression, which can be useful for treating, preventing, ameliorating, or slowing progression of a disease associated with such a target nucleic acid. In certain embodiments, the modified oligomeric compounds comprise antisense oligonucleotides that are gapmers having certain sugar motifs. In certain embodiments, the gapmer sugar motifs provided herein can be combined with any nucleobase sequence and any internucleoside linkage motif to form potent antisense oligonucleotides. 
     b. Certain Nucleobase Motifs 
     In certain embodiments, compounds described herein comprise oligonucleotides. In certain embodiments, oligonucleotides comprise modified and/or unmodified nucleobases arranged along the oligonucleotide or region thereof in a defined pattern or motif. In certain embodiments, each nucleobase is modified. In certain embodiments, none of the nucleobases are modified. In certain embodiments, each purine or each pyrimidine is modified. In certain embodiments, each adenine is modified. In certain embodiments, each guanine is modified. In certain embodiments, each thymine is modified. In certain embodiments, each uracil is modified. In certain embodiments, each cytosine is modified. In certain embodiments, some or all of the cytosine nucleobases in a modified oligonucleotide are 5-methylcytosines. 
     In certain embodiments, modified oligonucleotides comprise a block of modified nucleobases. In certain such embodiments, the block is at the 3′-end of the oligonucleotide. In certain embodiments the block is within 3 nucleosides of the 3′-end of the oligonucleotide. In certain embodiments, the block is at the 5′-end of the oligonucleotide. In certain embodiments the block is within 3 nucleosides of the 5′-end of the oligonucleotide. 
     In certain embodiments, oligonucleotides having a gapmer motif comprise a nucleoside comprising a modified nucleobase. In certain such embodiments, one nucleoside comprising a modified nucleobase is in the central gap of an oligonucleotide having a gapmer motif. In certain such embodiments, the sugar moiety of said nucleoside is a 2′-deoxyribosyl moiety. In certain embodiments, the modified nucleobase is selected from: a 2-thiopyrimidine and a 5-propynepyrimidine. 
     c. Certain Internucleoside Linkage Motifs 
     In certain embodiments, compounds described herein comprise oligonucleotides. In certain embodiments, oligonucleotides comprise modified and/or unmodified internucleoside linkages arranged along the oligonucleotide or region thereof in a defined pattern or motif. In certain embodiments, essentially each internucleoside linking group is a phosphate internucleoside linkage (P═O). In certain embodiments, each internucleoside linking group of a modified oligonucleotide is a phosphorothioate (P═S). In certain embodiments, each internucleoside linking group of a modified oligonucleotide is independently selected from a phosphorothioate and phosphate internucleoside linkage. In certain embodiments, the sugar motif of a modified oligonucleotide is a gapmer and the internucleoside linkages within the gap are all modified. In certain such embodiments, some or all of the internucleoside linkages in the wings are unmodified phosphate linkages. In certain embodiments, the terminal internucleoside linkages are modified. 
     4. Certain Modified Oligonucleotides 
     In certain embodiments, compounds described herein comprise modified oligonucleotides. In certain embodiments, the above modifications (sugar, nucleobase, internucleoside linkage) are incorporated into a modified oligonucleotide. In certain embodiments, modified oligonucleotides are characterized by their modification, motifs, and overall lengths. In certain embodiments, such parameters are each independent of one another. Thus, unless otherwise indicated, each internucleoside linkage of an oligonucleotide having a gapmer sugar motif may be modified or unmodified and may or may not follow the gapmer modification pattern of the sugar modifications. For example, the internucleoside linkages within the wing regions of a sugar gapmer may be the same or different from one another and may be the same or different from the internucleoside linkages of the gap region of the sugar motif. Likewise, such gapmer oligonucleotides may comprise one or more modified nucleobase independent of the gapmer pattern of the sugar modifications. Furthermore, in certain instances, an oligonucleotide is described by an overall length or range and by lengths or length ranges of two or more regions (e.g., a regions of nucleosides having specified sugar modifications), in such circumstances it may be possible to select numbers for each range that result in an oligonucleotide having an overall length falling outside the specified range. In such circumstances, both elements must be satisfied. For example, in certain embodiments, a modified oligonucleotide consists of 15-20 linked nucleosides and has a sugar motif consisting of three regions, A, B, and C, wherein region A consists of 2-6 linked nucleosides having a specified sugar motif, region B consists of 6-10 linked nucleosides having a specified sugar motif, and region C consists of 2-6 linked nucleosides having a specified sugar motif. Such embodiments do not include modified oligonucleotides where A and C each consist of 6 linked nucleosides and B consists of 10 linked nucleosides (even though those numbers of nucleosides are permitted within the requirements for A, B, and C) because the overall length of such oligonucleotide is 22, which exceeds the upper limit of the overall length of the modified oligonucleotide (20). Herein, if a description of an oligonucleotide is silent with respect to one or more parameter, such parameter is not limited. Thus, a modified oligonucleotide described only as having a gapmer sugar motif without further description may have any length, internucleoside linkage motif, and nucleobase motif. Unless otherwise indicated, all modifications are independent of nucleobase sequence. 
     Certain Conjugated Compounds 
     In certain embodiments, the compounds described herein comprise or consist of an oligonucleotide (modified or unmodified) and optionally one or more conjugate groups and/or terminal groups. Conjugate groups consist of one or more conjugate moiety and a conjugate linker which links the conjugate moiety to the oligonucleotide. Conjugate groups may be attached to either or both ends of an oligonucleotide and/or at any internal position. In certain embodiments, conjugate groups are attached to the 2′-position of a nucleoside of a modified oligonucleotide. In certain embodiments, conjugate groups that are attached to either or both ends of an oligonucleotide are terminal groups. In certain such embodiments, conjugate groups or terminal groups are attached at the 3′ and/or 5′-end of oligonucleotides. In certain such embodiments, conjugate groups (or terminal groups) are attached at the 3′-end of oligonucleotides. In certain embodiments, conjugate groups are attached near the 3′-end of oligonucleotides. In certain embodiments, conjugate groups (or terminal groups) are attached at the 5′-end of oligonucleotides. In certain embodiments, conjugate groups are attached near the 5′-end of oligonucleotides. 
     In certain embodiments, the oligonucleotide is modified. In certain embodiments, the oligonucleotide of a compound has a nucleobase sequence that is complementary to a target nucleic acid. In certain embodiments, oligonucleotides are complementary to a messenger RNA (mRNA). In certain embodiments, oligonucleotides are complementary to a sense transcript. 
     Examples of terminal groups include but are not limited to conjugate groups, capping groups, phosphate moieties, protecting groups, modified or unmodified nucleosides, and two or more nucleosides that are independently modified or unmodified. 
     Compositions and Methods for Formulating Pharmaceutical Compositions 
     Compounds described herein may be admixed with pharmaceutically acceptable active or inert substances for the preparation of pharmaceutical compositions or formulations. Compositions and methods for the formulation of pharmaceutical compositions are dependent upon a number of criteria, including, but not limited to, route of administration, extent of disease, or dose to be administered. 
     Certain embodiments provide pharmaceutical compositions comprising one or more compounds or a salt thereof. In certain embodiments, the compounds are antisense compounds or oligomeric compounds. In certain embodiments, the compounds comprise or consist of a modified oligonucleotide. In certain such embodiments, the pharmaceutical composition comprises a suitable pharmaceutically acceptable diluent or carrier. In certain embodiments, a pharmaceutical composition comprises a sterile saline solution and one or more compound. In certain embodiments, such pharmaceutical composition consists of a sterile saline solution and one or more compound. In certain embodiments, the sterile saline is pharmaceutical grade saline. In certain embodiments, a pharmaceutical composition comprises one or more compound and sterile water. In certain embodiments, a pharmaceutical composition consists of one compound and sterile water. In certain embodiments, the sterile water is pharmaceutical grade water. In certain embodiments, a pharmaceutical composition comprises one or more compound and phosphate-buffered saline (PBS). In certain embodiments, a pharmaceutical composition consists of one or more compound and sterile PBS. In certain embodiments, the sterile PBS is pharmaceutical grade PBS. Compositions and methods for the formulation of pharmaceutical compositions are dependent upon a number of criteria, including, but not limited to, route of administration, extent of disease, or dose to be administered. 
     A compound described herein targeted to SARS-CoV-2 RNA can be utilized in pharmaceutical compositions by combining the compound with a suitable pharmaceutically acceptable diluent or carrier. In certain embodiments, a pharmaceutically acceptable diluent is water, such as sterile water suitable for injection. Accordingly, in one embodiment, employed in the methods described herein is a pharmaceutical composition comprising a compound targeted to SARS-CoV-2 RNA and a pharmaceutically acceptable diluent. In certain embodiments, the pharmaceutically acceptable diluent is water. In certain embodiments, the compound comprises or consists of a modified oligonucleotide provided herein. 
     Pharmaceutical compositions comprising compounds provided herein encompass any pharmaceutically acceptable salts, esters, or salts of such esters, or any other oligonucleotide which, upon administration to an animal, including a human, is capable of providing (directly or indirectly) the biologically active metabolite or residue thereof. In certain embodiments, the compounds are antisense compounds or oligomeric compounds. In certain embodiments, the compound comprises or consists of a modified oligonucleotide. Accordingly, for example, the disclosure is also drawn to pharmaceutically acceptable salts of compounds, prodrugs, pharmaceutically acceptable salts of such prodrugs, and other bioequivalents. Suitable pharmaceutically acceptable salts include, but are not limited to, sodium and potassium salts. 
     A prodrug can include the incorporation of additional nucleosides at one or both ends of a compound which are cleaved by endogenous nucleases within the body, to form the active compound. 
     In certain embodiments, the compounds or compositions further comprise a pharmaceutically acceptable carrier or diluent. 
     EXAMPLES 
     Non-Limiting Disclosure and Incorporation by Reference 
     Although the sequence listing accompanying this filing identifies each sequence as either “RNA” or “DNA” as required, in reality, those sequences may be modified with any combination of chemical modifications. One of skill in the art will readily appreciate that such designation as “RNA” or “DNA” to describe modified oligonucleotides is, in certain instances, arbitrary. For example, an oligonucleotide comprising a nucleoside comprising a 2′-OH sugar moiety and a thymine base could be described as a DNA having a modified sugar (2′-OH for the natural 2′-H of DNA) or as an RNA having a modified base (thymine (methylated uracil) for natural uracil of RNA). 
     Accordingly, nucleic acid sequences provided herein, including, but not limited to those in the sequence listing, are intended to encompass nucleic acids containing any combination of natural or modified RNA and/or DNA, including, but not limited to such nucleic acids having modified nucleobases. By way of further example and without limitation, an oligonucleotide having the nucleobase sequence “ATCGATCG” encompasses any oligonucleotides having such nucleobase sequence, whether modified or unmodified, including, but not limited to, such compounds comprising RNA bases, such as those having sequence “AUCGAUCG” and those having some DNA bases and some RNA bases such as “AUCGATCG” and compounds having other modified nucleobases, such as “AT m CGAUCG,” wherein  m C indicates a cytosine base comprising a methyl group at the 5-position. 
     While certain compounds, compositions and methods described herein have been described with specificity in accordance with certain embodiments, the following examples serve only to illustrate the compounds described herein and are not intended to limit the same. Each of the references recited in the present application is incorporated herein by reference in its entirety. 
     Example 1: Design of Modified Oligonucleotides Complementary to a SARS-CoV-2 Nucleic Acid 
     Modified oligonucleotides were designed as indicated in the tables below. The modified oligonucleotides are all 3-10-3 cEt gapmers (i.e., they have a central gap segment of ten 2′-deoxynucleosides flanked on each side by wing segments, each comprising three cEt modified nucleosides). The internucleoside linkages throughout each modified oligonucleotide are phosphorothioate linkages. All cytosine nucleobases throughout each modified oligonucleotide are 5-methylcytosines. 
     “Start site” indicates the 5′-most nucleoside of the target sequence to which the modified oligonucleotide is complementary. “Stop site” indicates the 3′-most nucleoside of the target sequence to which the modified oligonucleotide is complementary. As shown in the tables below, the modified oligonucleotides are 100% complementary to the genomic sequence of severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, designated herein as SEQ ID NO: 1 (GENBANK Accession No. NC_045512.2). 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Design of 3-10-3 cEt modified oligonucleotides 
               
               
                 complementary to severe acute respiratory 
               
               
                 syndrome coronavirus 2 isolate Wuhan-Hu-1 
               
            
           
           
               
               
               
               
               
            
               
                   
                 SEQ 
                 SEQ 
                   
                   
               
               
                   
                 ID 
                 ID 
                   
                   
               
               
                   
                 NO: 
                 NO: 
                   
                   
               
               
                   
                 1 
                 1 
                   
                 SEQ 
               
               
                 Compound 
                 Start 
                 Stop 
                 Sequence 
                 ID 
               
               
                 Number 
                 Site 
                 Site 
                 (5&#39; to 3&#39;) 
                 NO 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 1495586 
                 191 
                 206 
                 GACGAAACCGTAAGCA 
                 3 
               
               
                   
               
               
                 1495640 
                 26344 
                 26359 
                 ATCGAAGCGCAGTAAG 
                 4 
               
               
                   
               
               
                 1495503 
                 13485 
                 13500 
                 TGTAAGACGGGCTGCA 
                 5 
               
               
                   
               
               
                 1495577 
                 17141 
                 17156 
                 GTATACACTATGCGAG 
                 6 
               
               
                   
               
               
                 1495616 
                 26248 
                 26263 
                 CCGAAACGAATGAGTA 
                 7 
               
               
                   
               
               
                 1495617 
                 26249 
                 26264 
                 TCCGAAACGAATGAGT 
                 8 
               
               
                   
               
               
                 1495623 
                 26284 
                 26299 
                 GAAGTACGCTATTAAC 
                 9 
               
               
                   
               
               
                 1495672 
                 29242 
                 29257 
                 TCCCGAAGGTGTGACT 
                 10 
               
               
                   
               
               
                 1495615 
                 26247 
                 26262 
                 CGAAACGAATGAGTAC 
                 11 
               
               
                   
               
               
                 1495642 
                 26349 
                 26364 
                 ACACAATCGAAGCGCA 
                 12 
               
               
                   
               
               
                 1495668 
                 28521 
                 28536 
                 CGGTAGTAGCCAATTT 
                 13 
               
               
                   
               
               
                 1495701 
                 635 
                 650 
                 TATTACCGTTCTTACG 
                 14 
               
               
                   
               
               
                 1495576 
                 17140 
                 17155 
                 TATACACTATGCGAGC 
                 15 
               
               
                   
               
               
                 1495597 
                 237 
                 252 
                 CACACCCGGACGAAAC 
                 16 
               
               
                   
               
               
                 1495607 
                 25509 
                 25524 
                 TCCGAAAGGGAGTGAG 
                 17 
               
               
                   
               
               
                 1495641 
                 26348 
                 26363 
                 CACAATCGAAGCGCAG 
                 18 
               
               
                   
               
               
                 1495673 
                 29243 
                 29258 
                 TTCCCGAAGGTGTGAC 
                 19 
               
               
                   
               
               
                 1495703 
                 6467 
                 6482 
                 CTACAACTTCGGTAGT 
                 20 
               
               
                   
               
               
                 1495527 
                 15010 
                 15025 
                 CGAAAAGTGCATCTTG 
                 21 
               
               
                   
               
               
                 1495528 
                 15011 
                 15026 
                 GCGAAAAGTGCATCTT 
                 22 
               
               
                   
               
               
                 1495665 
                 28417 
                 28432 
                 GAACCAAGACGCAGTA 
                 23 
               
               
                   
               
               
                 1495478 
                 11435 
                 11450 
                 GATCTAAAGCATTACC 
                 24 
               
               
                   
               
               
                 1495497 
                 13371 
                 13386 
                 CCGCAGACGGTACAGA 
                 25 
               
               
                   
               
               
                 1495500 
                 13458 
                 13473 
                 AACCCGTTTAAAAACG 
                 26 
               
               
                   
               
               
                 1495513 
                 14667 
                 14682 
                 ATTACCGGGTTTGACA 
                 27 
               
               
                   
               
               
                 1495575 
                 17137 
                 17152 
                 ACACTATGCGAGCAGA 
                 28 
               
               
                   
               
               
                 1495585 
                 190 
                 205 
                 ACGAAACCGTAAGCAG 
                 29 
               
               
                   
               
               
                 1495608 
                 25510 
                 25525 
                 ATCCGAAAGGGAGTGA 
                 30 
               
               
                   
               
               
                 1495483 
                 12841 
                 12856 
                 AGGGAATCTAGCCCAT 
                 31 
               
               
                   
               
               
                 1495514 
                 14668 
                 14683 
                 AATTACCGGGTTTGAC 
                 32 
               
               
                   
               
               
                 1495639 
                 26338 
                 26353 
                 GCGCAGTAAGGATGGC 
                 33 
               
               
                   
               
               
                 1495663 
                 28415 
                 28430 
                 ACCAAGACGCAGTATT 
                 34 
               
               
                   
               
               
                 1495664 
                 28416 
                 28431 
                 AACCAAGACGCAGTAT 
                 35 
               
               
                   
               
               
                 1495670 
                 28812 
                 28827 
                 CGAGAAGAGGCTTGAC 
                 36 
               
               
                   
               
               
                 1495671 
                 29241 
                 29256 
                 CCCGAAGGTGTGACTT 
                 37 
               
               
                   
               
               
                 1495613 
                 26206 
                 26221 
                 CTTACAAAGGCACGCT 
                 38 
               
               
                   
               
               
                 1495622 
                 26283 
                 26298 
                 AAGTACGCTATTAACT 
                 39 
               
               
                   
               
               
                 1495515 
                 14669 
                 14684 
                 AAATTACCGGGTTTGA 
                 40 
               
               
                   
               
               
                 1495566 
                 15991 
                 16006 
                 TCATAAGTGTACCATC 
                 41 
               
               
                   
               
               
                 1495612 
                 26205 
                 26220 
                 TTACAAAGGCACGCTA 
                 42 
               
               
                   
               
               
                 1495619 
                 26278 
                 26293 
                 CGCTATTAACTATTAA 
                 43 
               
               
                   
               
               
                 1495646 
                 26374 
                 26389 
                 CGTTAACAATATTGCA 
                 44 
               
               
                   
               
               
                 1495518 
                 14672 
                 14687 
                 TTAAAATTACCGGGTT 
                 45 
               
               
                   
               
               
                 1495558 
                 15846 
                 15861 
                 TTTAGTAAGGTCAGTC 
                 46 
               
               
                   
               
               
                 1495564 
                 15889 
                 15904 
                 GTTTAACTAGCATTGT 
                 47 
               
               
                   
               
               
                 1495632 
                 26307 
                 26322 
                 GAATACCACGAAAGCA 
                 48 
               
               
                   
               
               
                 1495662 
                 28409 
                 28424 
                 ACGCAGTATTATTGGG 
                 49 
               
               
                   
               
               
                 1495679 
                 29617 
                 29632 
                 GTTACGAGAATTCATT 
                 50 
               
               
                   
               
               
                 1495688 
                 29781 
                 29796 
                 TCCATATAGGCAGCTC 
                 51 
               
               
                   
               
               
                 1495702 
                 6464 
                 6479 
                 CAACTTCGGTAGTTTT 
                 52 
               
               
                   
               
               
                 1495517 
                 14671 
                 14686 
                 TAAAATTACCGGGTTT 
                 53 
               
               
                   
               
               
                 1495534 
                 15074 
                 15089 
                 GCACTAATGGCATACT 
                 54 
               
               
                   
               
               
                 1495560 
                 15848 
                 15863 
                 CCTTTAGTAAGGTCAG 
                 55 
               
               
                   
               
               
                 1495625 
                 26287 
                 26302 
                 AAAGAAGTACGCTATT 
                 56 
               
               
                   
               
               
                 1495676 
                 29613 
                 29628 
                 CGAGAATTCATTCTGC 
                 57 
               
               
                   
               
               
                 1495681 
                 29619 
                 29634 
                 TAGTTACGAGAATTCA 
                 58 
               
               
                   
               
               
                 1495690 
                 29794 
                 29809 
                 ACATTAGGGCTCTTCC 
                 59 
               
               
                   
               
               
                 1495546 
                 15500 
                 15515 
                 CTATTAGCATAAGCAG 
                 60 
               
               
                   
               
               
                 1495548 
                 15502 
                 15517 
                 CACTATTAGCATAAGC 
                 61 
               
               
                   
               
               
                 1495611 
                 26204 
                 26219 
                 TACAAAGGCACGCTAG 
                 62 
               
               
                   
               
               
                 1495624 
                 26286 
                 26301 
                 AAGAAGTACGCTATTA 
                 63 
               
               
                   
               
               
                 1495529 
                 15043 
                 15058 
                 TTATAGTAGGGATGAC 
                 64 
               
               
                   
               
               
                 1495531 
                 15046 
                 15061 
                 GAGTTATAGTAGGGAT 
                 65 
               
               
                   
               
               
                 1495543 
                 15283 
                 15298 
                 GATAATCCCAACCCAT 
                 66 
               
               
                   
               
               
                 1495556 
                 15844 
                 15859 
                 TAGTAAGGTCAGTCTC 
                 67 
               
               
                   
               
               
                 1495565 
                 15990 
                 16005 
                 CATAAGTGTACCATCT 
                 68 
               
               
                   
               
               
                 1495594 
                 20946 
                 20961 
                 ATTAAGATCTGAATCG 
                 69 
               
               
                   
               
               
                 1495620 
                 26279 
                 26294 
                 ACGCTATTAACTATTA 
                 70 
               
               
                   
               
               
                 1495628 
                 26290 
                 26305 
                 GAAAAAGAAGTACGCT 
                 71 
               
               
                   
               
               
                 1495649 
                 26579 
                 26594 
                 TATTACTAGGTTCCAT 
                 72 
               
               
                   
               
               
                 1495697 
                 458 
                 473 
                 ACACATAGGGCTGTTC 
                 73 
               
               
                   
               
               
                 1495494 
                 12974 
                 12989 
                 CCATACCTCTATTTAG 
                 74 
               
               
                   
               
               
                 1495544 
                 15496 
                 15511 
                 TAGCATAAGCAGTTGT 
                 75 
               
               
                   
               
               
                 1495568 
                 15994 
                 16009 
                 CAATCATAAGTGTACC 
                 76 
               
               
                   
               
               
                 1495626 
                 26288 
                 26303 
                 AAAAGAAGTACGCTAT 
                 77 
               
               
                   
               
               
                 1495633 
                 26308 
                 26323 
                 AGAATACCACGAAAGC 
                 78 
               
               
                   
               
               
                 1495650 
                 26580 
                 26595 
                 CTATTACTAGGTTCCA 
                 79 
               
               
                   
               
               
                 1495489 
                 12893 
                 12908 
                 ACCTACAAGGTGGTTC 
                 80 
               
               
                   
               
               
                 1495506 
                 13769 
                 13784 
                 GATATATGTGGTACCA 
                 81 
               
               
                   
               
               
                 1495508 
                 14404 
                 14419 
                 CAAAACTTGTAGGTGG 
                 82 
               
               
                   
               
               
                 1495553 
                 15625 
                 15640 
                 TTCTATAGAGACACTC 
                 83 
               
               
                   
               
               
                 1495605 
                 25507 
                 25522 
                 CGAAAGGGAGTGAGGC 
                 84 
               
               
                   
               
               
                 1495647 
                 26576 
                 26591 
                 TACTAGGTTCCATTGT 
                 85 
               
               
                   
               
               
                 1495651 
                 26582 
                 26597 
                 ACCTATTACTAGGTTC 
                 86 
               
               
                   
               
               
                 1495653 
                 26585 
                 26600 
                 GAAACCTATTACTAGG 
                 87 
               
               
                   
               
               
                 1495677 
                 29615 
                 29630 
                 TACGAGAATTCATTCT 
                 88 
               
               
                   
               
               
                 1495691 
                 29795 
                 29810 
                 CACATTAGGGCTCTTC 
                 89 
               
               
                   
               
               
                 1495695 
                 306 
                 321 
                 GGCAAACTGAGTTGGA 
                 90 
               
               
                   
               
               
                 1495488 
                 12892 
                 12907 
                 CCTACAAGGTGGTTCC 
                 91 
               
               
                   
               
               
                 1495516 
                 14670 
                 14685 
                 AAAATTACCGGGTTTG 
                 92 
               
               
                   
               
               
                 1495520 
                 14889 
                 14904 
                 AATACAGCCACCATCG 
                 93 
               
               
                   
               
               
                 1495557 
                 15845 
                 15860 
                 TTAGTAAGGTCAGTCT 
                 94 
               
               
                   
               
               
                 1495559 
                 15847 
                 15862 
                 CTTTAGTAAGGTCAGT 
                 95 
               
               
                   
               
               
                 1495584 
                 18890 
                 18905 
                 CGCTTAACAAAGCACT 
                 96 
               
               
                   
               
               
                 1495593 
                 20324 
                 20339 
                 AAATCTCCATAAACGA 
                 97 
               
               
                   
               
               
                 1495610 
                 26203 
                 26218 
                 ACAAAGGCACGCTAGT 
                 98 
               
               
                   
               
               
                 1495667 
                 28518 
                 28533 
                 TAGTAGCCAATTTGGT 
                 99 
               
               
                   
               
               
                 1495678 
                 29616 
                 29631 
                 TTACGAGAATTCATTC 
                 100 
               
               
                   
               
               
                 1495680 
                 29618 
                 29633 
                 AGTTACGAGAATTCAT 
                 101 
               
               
                   
               
               
                 1495687 
                 29780 
                 29795 
                 CCATATAGGCAGCTCT 
                 102 
               
               
                   
               
               
                 1495692 
                 29796 
                 29811 
                 ACACATTAGGGCTCTT 
                 103 
               
               
                   
               
               
                 1495693 
                 29800 
                 29815 
                 TTTTACACATTAGGGC 
                 104 
               
               
                   
               
               
                 1495694 
                 305 
                 320 
                 GCAAACTGAGTTGGAC 
                 105 
               
               
                   
               
               
                 1495484 
                 12845 
                 12860 
                 TCTTAGGGAATCTAGC 
                 106 
               
               
                   
               
               
                 1495486 
                 12890 
                 12905 
                 TACAAGGTGGTTCCAG 
                 107 
               
               
                   
               
               
                 1495487 
                 12891 
                 12906 
                 CTACAAGGTGGTTCCA 
                 108 
               
               
                   
               
               
                 1495504 
                 13510 
                 13525 
                 CAGTACTAGTGCCTGT 
                 109 
               
               
                   
               
               
                 1495509 
                 14405 
                 14420 
                 CCAAAACTTGTAGGTG 
                 110 
               
               
                   
               
               
                 1495523 
                 14969 
                 14984 
                 TAAAGTCTAGCCTTAC 
                 111 
               
               
                   
               
               
                 1495542 
                 15278 
                 15293 
                 TCCCAACCCATAAGGT 
                 112 
               
               
                   
               
               
                 1495573 
                 17085 
                 17100 
                 CTTACCAGTACCAGGT 
                 113 
               
               
                   
               
               
                 1495502 
                 13461 
                 13476 
                 GCAAACCCGTTTAAAA 
                 114 
               
               
                   
               
               
                 1495507 
                 14050 
                 14065 
                 TATCTAATGTCAGTAC 
                 115 
               
               
                   
               
               
                 1495510 
                 14407 
                 14422 
                 GTCCAAAACTTGTAGG 
                 116 
               
               
                   
               
               
                 1495525 
                 14973 
                 14988 
                 ATAATAAAGTCTAGCC 
                 117 
               
               
                   
               
               
                 1495570 
                 16200 
                 16215 
                 GTACATAGCCTCATAA 
                 118 
               
               
                   
               
               
                 1495606 
                 25508 
                 25523 
                 CCGAAAGGGAGTGAGG 
                 119 
               
               
                   
               
               
                 1495643 
                 26367 
                 26382 
                 AATATTGCAGCAGTAC 
                 120 
               
               
                   
               
               
                 1495656 
                 27517 
                 27532 
                 GAAATGGTGAATTGCC 
                 121 
               
               
                   
               
               
                 1495669 
                 28745 
                 28760 
                 GAGGAAGTTGTAGCAC 
                 122 
               
               
                   
               
               
                 1495485 
                 12846 
                 12861 
                 CTCTTAGGGAATCTAG 
                 123 
               
               
                   
               
               
                 1495561 
                 15886 
                 15901 
                 TAACTAGCATTGTATG 
                 124 
               
               
                   
               
               
                 1495602 
                 24620 
                 24635 
                 CAAGATTAGCAGAAGC 
                 125 
               
               
                   
               
               
                 1495630 
                 26304 
                 26319 
                 TACCACGAAAGCAAGA 
                 126 
               
               
                   
               
               
                 1495658 
                 28402 
                 28417 
                 ATTATTGGGTAAACCT 
                 127 
               
               
                   
               
               
                 1495661 
                 28406 
                 28421 
                 CAGTATTATTGGGTAA 
                 128 
               
               
                   
               
               
                 1495689 
                 29782 
                 29797 
                 TTCCATATAGGCAGCT 
                 129 
               
               
                   
               
               
                 1495699 
                 460 
                 475 
                 GAACACATAGGGCTGT 
                 130 
               
               
                   
               
               
                 1495471 
                 10412 
                 10427 
                 CACCAGATGGTGAACC 
                 131 
               
               
                   
               
               
                 1495490 
                 12894 
                 12909 
                 AACCTACAAGGTGGTT 
                 132 
               
               
                   
               
               
                 1495533 
                 15073 
                 15088 
                 CACTAATGGCATACTT 
                 133 
               
               
                   
               
               
                 1495574 
                 17096 
                 17111 
                 GCAAAATGACTCTTAC 
                 134 
               
               
                   
               
               
                 1495590 
                 19832 
                 19847 
                 CCCAAATTATTGAGTA 
                 135 
               
               
                   
               
               
                 1495629 
                 26291 
                 26306 
                 AGAAAAAGAAGTACGC 
                 136 
               
               
                   
               
               
                 1495631 
                 26306 
                 26321 
                 AATACCACGAAAGCAA 
                 137 
               
               
                   
               
               
                 1495636 
                 26334 
                 26349 
                 AGTAAGGATGGCTAGT 
                 138 
               
               
                   
               
               
                 1495654 
                 26587 
                 26602 
                 AGGAAACCTATTACTA 
                 139 
               
               
                   
               
               
                 1495674 
                 29598 
                 29613 
                 CACAAGAGTAGACTAT 
                 140 
               
               
                   
               
               
                 1495522 
                 14894 
                 14909 
                 GCATTAATACAGCCAC 
                 141 
               
               
                   
               
               
                 1495524 
                 14972 
                 14987 
                 TAATAAAGTCTAGCCT 
                 142 
               
               
                   
               
               
                 1495567 
                 15992 
                 16007 
                 ATCATAAGTGTACCAT 
                 143 
               
               
                   
               
               
                 1495581 
                 18197 
                 18212 
                 ATCATAGAGATGAGTC 
                 144 
               
               
                   
               
               
                 1495587 
                 19580 
                 19595 
                 AGGTTATAAGTATCAA 
                 145 
               
               
                   
               
               
                 1495618 
                 26276 
                 26291 
                 CTATTAACTATTAACG 
                 146 
               
               
                   
               
               
                 1495637 
                 26335 
                 26350 
                 CAGTAAGGATGGCTAG 
                 147 
               
               
                   
               
               
                 1495521 
                 14893 
                 14908 
                 CATTAATACAGCCACC 
                 148 
               
               
                   
               
               
                 1495530 
                 15045 
                 15060 
                 AGTTATAGTAGGGATG 
                 149 
               
               
                   
               
               
                 1495540 
                 15122 
                 15137 
                 ATAGTACTACAGATAG 
                 150 
               
               
                   
               
               
                 1495541 
                 15124 
                 15139 
                 TCATAGTACTACAGAT 
                 151 
               
               
                   
               
               
                 1495547 
                 15501 
                 15516 
                 ACTATTAGCATAAGCA 
                 152 
               
               
                   
               
               
                 1495552 
                 15624 
                 15639 
                 TCTATAGAGACACTCA 
                 153 
               
               
                   
               
               
                 1495572 
                 17083 
                 17098 
                 TACCAGTACCAGGTGG 
                 154 
               
               
                   
               
               
                 1495621 
                 26280 
                 26295 
                 TACGCTATTAACTATT 
                 155 
               
               
                   
               
               
                 1495652 
                 26583 
                 26598 
                 AACCTATTACTAGGTT 
                 156 
               
               
                   
               
               
                 1495666 
                 28514 
                 28529 
                 AGCCAATTTGGTCATC 
                 157 
               
               
                   
               
               
                 1495700 
                 627 
                 642 
                 TTCTTACGAAGAAGAA 
                 158 
               
               
                   
               
               
                 1495476 
                 10739 
                 10754 
                 CCACAAGGTTAAAGTC 
                 159 
               
               
                   
               
               
                 1495481 
                 12287 
                 12302 
                 ACATTTGGGTCATAGC 
                 160 
               
               
                   
               
               
                 1495493 
                 12968 
                 12983 
                 CTCTATTTAGGTTGTT 
                 161 
               
               
                   
               
               
                 1495526 
                 14974 
                 14989 
                 CATAATAAAGTCTAGC 
                 162 
               
               
                   
               
               
                 1495609 
                 25802 
                 25817 
                 TCATAAAGTAATGGGT 
                 163 
               
               
                   
               
               
                 1495645 
                 26373 
                 26388 
                 GTTAACAATATTGCAG 
                 164 
               
               
                   
               
               
                 1495659 
                 28403 
                 28418 
                 TATTATTGGGTAAACC 
                 165 
               
               
                   
               
               
                 1495498 
                 13397 
                 13412 
                 AACTACAGCCATAACC 
                 166 
               
               
                   
               
               
                 1495537 
                 15119 
                 15134 
                 GTACTACAGATAGAGA 
                 167 
               
               
                   
               
               
                 1328721 
                 15843 
                 15858 
                 AGTAAGGTCAGTCTCA 
                 168 
               
               
                   
               
               
                 1495599 
                 24449 
                 24464 
                 AGCTAAGTTGTTTAAC 
                 169 
               
               
                   
               
               
                 1495600 
                 24450 
                 24465 
                 GAGCTAAGTTGTTTAA 
                 170 
               
               
                   
               
               
                 1495638 
                 26336 
                 26351 
                 GCAGTAAGGATGGCTA 
                 171 
               
               
                   
               
               
                 1495660 
                 28404 
                 28419 
                 GTATTATTGGGTAAAC 
                 172 
               
               
                   
               
               
                 1495686 
                 29779 
                 29794 
                 CATATAGGCAGCTCTC 
                 173 
               
               
                   
               
               
                 1495696 
                 456 
                 471 
                 ACATAGGGCTGTTCAA 
                 174 
               
               
                   
               
               
                 1495473 
                 10416 
                 10431 
                 TAAACACCAGATGGTG 
                 175 
               
               
                   
               
               
                 1495479 
                 11436 
                 11451 
                 TGATCTAAAGCATTAC 
                 176 
               
               
                   
               
               
                 1495482 
                 12587 
                 12602 
                 CACTAAGTTGAACAAT 
                 177 
               
               
                   
               
               
                 1495495 
                 13272 
                 13287 
                 CCTTTAGGATTTGGAT 
                 178 
               
               
                   
               
               
                 1495505 
                 13768 
                 13783 
                 ATATATGTGGTACCAT 
                 179 
               
               
                   
               
               
                 1495539 
                 15121 
                 15136 
                 TAGTACTACAGATAGA 
                 180 
               
               
                   
               
               
                 1495554 
                 15686 
                 15701 
                 GAGAAATGTTTACGCA 
                 181 
               
               
                   
               
               
                 1495578 
                 17956 
                 17971 
                 TATCAGACATTATGCA 
                 182 
               
               
                   
               
               
                 1495582 
                 18203 
                 18218 
                 AAACCCATCATAGAGA 
                 183 
               
               
                   
               
               
                 1495474 
                 10484 
                 10499 
                 CAACACTACCACATGA 
                 184 
               
               
                   
               
               
                 1495512 
                 14516 
                 14531 
                 GAGCTATGTAAGTTTA 
                 185 
               
               
                   
               
               
                 1495538 
                 15120 
                 15135 
                 AGTACTACAGATAGAG 
                 186 
               
               
                   
               
               
                 1495551 
                 15623 
                 15638 
                 CTATAGAGACACTCAT 
                 187 
               
               
                   
               
               
                 1495571 
                 16436 
                 16451 
                 CAATAATAGCTCATAC 
                 188 
               
               
                   
               
               
                 1495579 
                 17959 
                 17974 
                 CTCTATCAGACATTAT 
                 189 
               
               
                   
               
               
                 1495596 
                 23677 
                 23692 
                 GTTATTAGAGTAAGCA 
                 190 
               
               
                   
               
               
                 1495604 
                 24663 
                 24678 
                 CTTTTTGATTGTCCAA 
                 191 
               
               
                   
               
               
                 1495635 
                 26310 
                 26325 
                 CAAGAATACCACGAAA 
                 192 
               
               
                   
               
               
                 1495648 
                 26578 
                 26593 
                 ATTACTAGGTTCCATT 
                 193 
               
               
                   
               
               
                 1495704 
                 7536 
                 7551 
                 CCATTAACAATAGTTG 
                 194 
               
               
                   
               
               
                 1495492 
                 12896 
                 12911 
                 CAAACCTACAAGGTGG 
                 195 
               
               
                   
               
               
                 1495499 
                 13398 
                 13413 
                 CAACTACAGCCATAAC 
                 196 
               
               
                   
               
               
                 1495519 
                 14854 
                 14869 
                 CAACAACTTCAACTAC 
                 197 
               
               
                   
               
               
                 1495535 
                 15110 
                 15125 
                 ATAGAGACACCAGCTA 
                 198 
               
               
                   
               
               
                 1495549 
                 15503 
                 15518 
                 ACACTATTAGCATAAG 
                 199 
               
               
                   
               
               
                 1495562 
                 15887 
                 15902 
                 TTAACTAGCATTGTAT 
                 200 
               
               
                   
               
               
                 1495591 
                 19833 
                 19848 
                 ACCCAAATTATTGAGT 
                 201 
               
               
                   
               
               
                 1495592 
                 20113 
                 20128 
                 CTCCAATTAATGTGAC 
                 202 
               
               
                   
               
               
                 1495598 
                 24448 
                 24463 
                 GCTAAGTTGTTTAACA 
                 203 
               
               
                   
               
               
                 1495634 
                 26309 
                 26324 
                 AAGAATACCACGAAAG 
                 204 
               
               
                   
               
               
                 1495480 
                 11837 
                 11852 
                 ACATTTTAGACTGTAC 
                 205 
               
               
                   
               
               
                 1495501 
                 13459 
                 13474 
                 AAACCCGTTTAAAAAC 
                 206 
               
               
                   
               
               
                 1495511 
                 14515 
                 14530 
                 AGCTATGTAAGTTTAC 
                 207 
               
               
                   
               
               
                 1495536 
                 15118 
                 15133 
                 TACTACAGATAGAGAC 
                 208 
               
               
                   
               
               
                 1495580 
                 18196 
                 18211 
                 TCATAGAGATGAGTCT 
                 209 
               
               
                   
               
               
                 1495589 
                 19781 
                 19796 
                 GCCCAAAGCTCAAATG 
                 210 
               
               
                   
               
               
                 1495595 
                 20947 
                 20962 
                 CATTAAGATCTGAATC 
                 211 
               
               
                   
               
               
                 1495614 
                 26244 
                 26259 
                 AACGAATGAGTACATA 
                 212 
               
               
                   
               
               
                 1495655 
                 27165 
                 27180 
                 GCAAAGCAATATTGTC 
                 213 
               
               
                   
               
               
                 1495675 
                 29599 
                 29614 
                 GCACAAGAGTAGACTA 
                 214 
               
               
                   
               
               
                 1495698 
                 459 
                 474 
                 AACACATAGGGCTGTT 
                 215 
               
               
                   
               
               
                 1495496 
                 13274 
                 13289 
                 ATCCTTTAGGATTTGG 
                 216 
               
               
                   
               
               
                 1495550 
                 15622 
                 15637 
                 TATAGAGACACTCATA 
                 217 
               
               
                   
               
               
                 1495569 
                 16051 
                 16066 
                 CCTGATTAGGATGTTT 
                 218 
               
               
                   
               
               
                 1495603 
                 24621 
                 24636 
                 GCAAGATTAGCAGAAG 
                 219 
               
               
                   
               
               
                 1495644 
                 26368 
                 26383 
                 CAATATTGCAGCAGTA 
                 220 
               
               
                   
               
               
                 1495685 
                 29778 
                 29793 
                 ATATAGGCAGCTCTCC 
                 221 
               
               
                   
               
               
                 1495477 
                 11432 
                 11447 
                 CTAAAGCATTACCATA 
                 222 
               
               
                   
               
               
                 1495491 
                 12895 
                 12910 
                 AAACCTACAAGGTGGT 
                 223 
               
               
                   
               
               
                 1495532 
                 15072 
                 15087 
                 ACTAATGGCATACTTA 
                 224 
               
               
                   
               
               
                 1495545 
                 15499 
                 15514 
                 TATTAGCATAAGCAGT 
                 225 
               
               
                   
               
               
                 1495588 
                 19780 
                 19795 
                 CCCAAAGCTCAAATGC 
                 226 
               
               
                   
               
               
                 1495601 
                 24474 
                 24489 
                 ACACTTGAAATTGCAC 
                 227 
               
               
                   
               
               
                 1495657 
                 27518 
                 27533 
                 TGAAATGGTGAATTGC 
                 228 
               
               
                   
               
               
                 1495682 
                 29668 
                 29683 
                 TAAAGATTGCTATGTG 
                 229 
               
               
                   
               
               
                 1495683 
                 29671 
                 29686 
                 GATTAAAGATTGCTAT 
                 230 
               
               
                   
               
               
                 1495472 
                 10414 
                 10429 
                 AACACCAGATGGTGAA 
                 231 
               
               
                   
               
               
                 1495475 
                 10491 
                 10506 
                 TTAAAACCAACACTAC 
                 232 
               
               
                   
               
               
                 1495563 
                 15888 
                 15903 
                 TTTAACTAGCATTGTA 
                 233 
               
               
                   
               
               
                 1495583 
                 18889 
                 18904 
                 GCTTAACAAAGCACTC 
                 234 
               
               
                   
               
               
                 1495627 
                 26289 
                 26304 
                 AAAAAGAAGTACGCTA 
                 235 
               
               
                   
               
               
                 1495684 
                 29689 
                 29704 
                 TCCCTAATGTTACACA 
                 236 
               
               
                   
               
            
           
         
       
     
     Modified oligonucleotides were designed as indicated in the tables below. The modified oligonucleotides are all 3-10-3 cEt gapmers (i.e., they have a central gap segment of ten 2′-deoxynucleosides flanked on each side by wing segments, each comprising three cEt modified nucleosides). The internucleoside linkages throughout each modified oligonucleotide are phosphorothioate linkages. All cytosine nucleobases throughout each modified oligonucleotide are 5-methylcytosines. 
     “Start site” indicates the 5′-most nucleoside of the target sequence to which the modified oligonucleotide is complementary. “Stop site” indicates the 3′-most nucleoside of the target sequence to which the modified oligonucleotide is complementary. As shown in the tables below, the modified oligonucleotides are 100% complementary to the complement of genomic sequence of severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, designated herein as SEQ ID NO: 2 (the complement of GENBANK Accession No. NC_045512.2). 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Design of 3-10-3 cET modified oligonucleotides 
               
               
                 complementary to the complement of severe 
               
               
                 acute respiratory syndrome coronavirus 2 
               
               
                 isolate Wuhan-Hu-1 
               
            
           
           
               
               
               
               
               
            
               
                   
                 SEQ 
                 SEQ 
                   
                   
               
               
                   
                 ID 
                 ID 
                   
                   
               
               
                   
                 NO: 
                 NO: 
                   
                   
               
               
                   
                 2 
                 2 
                   
                 SEQ 
               
               
                 Compound 
                 Start 
                 Stop 
                 Sequence 
                 ID 
               
               
                 Number 
                 Site 
                 Site 
                 (5&#39; to 3&#39;) 
                 NO 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 1495797 
                 11627 
                 11642 
                 ACCCGCGAAGAAGCTA 
                 237 
               
               
                   
               
               
                 1495798 
                 11628 
                 11643 
                 CACCCGCGAAGAAGCT 
                 238 
               
               
                   
               
               
                 1495810 
                 1358 
                 1373 
                 CTACCGAAGAGCTACC 
                 239 
               
               
                   
               
               
                 1495895 
                 16425 
                 16440 
                 TAAACGGGTTTGCGGT 
                 240 
               
               
                   
               
               
                 1495897 
                 16427 
                 16442 
                 TTTAAACGGGTTTGCG 
                 241 
               
               
                   
               
               
                 1495927 
                 23422 
                 23437 
                 ACTACCGAAGTTGTAG 
                 242 
               
               
                   
               
               
                 1495894 
                 16424 
                 16439 
                 AAACGGGTTTGCGGTG 
                 243 
               
               
                   
               
               
                 1495896 
                 16426 
                 16441 
                 TTAAACGGGTTTGCGG 
                 244 
               
               
                   
               
               
                 1495926 
                 23421 
                 23436 
                 CTACCGAAGTTGTAGG 
                 245 
               
               
                   
               
               
                 1495928 
                 23423 
                 23438 
                 AACTACCGAAGTTGTA 
                 246 
               
               
                   
               
               
                 1495796 
                 11626 
                 11641 
                 CCCGCGAAGAAGCTAT 
                 247 
               
               
                   
               
               
                 1495842 
                 1481 
                 1496 
                 ACCCAATAATACTGCG 
                 248 
               
               
                   
               
               
                 1495947 
                 29254 
                 29269 
                 CGTAAGAACGGTAATA 
                 249 
               
               
                   
               
               
                 1495971 
                 4786 
                 4801 
                 AAAGAAATTGACCGCC 
                 250 
               
               
                   
               
               
                 1495986 
                 722 
                 737 
                 CAAACATTGGCCGCAA 
                 251 
               
               
                   
               
               
                 1495811 
                 1359 
                 1374 
                 ACTACCGAAGAGCTAC 
                 252 
               
               
                   
               
               
                 1495901 
                 16431 
                 16446 
                 CGTTTTTAAACGGGTT 
                 253 
               
               
                   
               
               
                 1495940 
                 2382 
                 2397 
                 AACATACGAGGGCAAT 
                 254 
               
               
                   
               
               
                 1496011 
                 9422 
                 9437 
                 GCGCAAACAGGTTCAT 
                 255 
               
               
                   
               
               
                 1495792 
                 1113 
                 1128 
                 CAAAAGGCTTCTACGC 
                 256 
               
               
                   
               
               
                 1495855 
                 14800 
                 14815 
                 CAAAGAATAGAGCTCG 
                 257 
               
               
                   
               
               
                 1495938 
                 2380 
                 2395 
                 CATACGAGGGCAATTC 
                 258 
               
               
                   
               
               
                 1495967 
                 4782 
                 4797 
                 AAATTGACCGCCTCAA 
                 259 
               
               
                   
               
               
                 1495968 
                 4783 
                 4798 
                 GAAATTGACCGCCTCA 
                 260 
               
               
                   
               
               
                 1496016 
                 9434 
                 9449 
                 TTCATAACAGATGCGC 
                 261 
               
               
                   
               
               
                 1495851 
                 14796 
                 14811 
                 GAATAGAGCTCGCACC 
                 262 
               
               
                   
               
               
                 1495852 
                 14797 
                 14812 
                 AGAATAGAGCTCGCAC 
                 263 
               
               
                   
               
               
                 1495936 
                 2378 
                 2393 
                 TACGAGGGCAATTCAC 
                 264 
               
               
                   
               
               
                 1495996 
                 103 
                 118 
                 GCCTATATGGAAGAGC 
                 265 
               
               
                   
               
               
                 1496010 
                 9421 
                 9436 
                 CGCAAACAGGTTCATC 
                 266 
               
               
                   
               
               
                 1495812 
                 1360 
                 1375 
                 TACTACCGAAGAGCTA 
                 267 
               
               
                   
               
               
                 1495847 
                 14708 
                 14723 
                 GCCACTAGAGGAGCTA 
                 268 
               
               
                   
               
               
                 1495875 
                 15220 
                 15235 
                 TCAAACCCGGTAATTT 
                 269 
               
               
                   
               
               
                 1495877 
                 15283 
                 15298 
                 TAGATAAACGCACTAC 
                 270 
               
               
                   
               
               
                 1495898 
                 16428 
                 16443 
                 TTTTAAACGGGTTTGC 
                 271 
               
               
                   
               
               
                 1495913 
                 17182 
                 17197 
                 GCACTACGACAGATGT 
                 272 
               
               
                   
               
               
                 1495939 
                 2381 
                 2396 
                 ACATACGAGGGCAATT 
                 273 
               
               
                   
               
               
                 1495969 
                 4784 
                 4799 
                 AGAAATTGACCGCCTC 
                 274 
               
               
                   
               
               
                 1496015 
                 9433 
                 9448 
                 TCATAACAGATGCGCA 
                 275 
               
               
                   
               
               
                 1495814 
                 1361 
                 1376 
                 CTACTACCGAAGAGCT 
                 276 
               
               
                   
               
               
                 1495815 
                 1369 
                 1384 
                 CAAATTGGCTACTACC 
                 277 
               
               
                   
               
               
                 1495816 
                 1370 
                 1385 
                 CCAAATTGGCTACTAC 
                 278 
               
               
                   
               
               
                 1495876 
                 15227 
                 15242 
                 CAAACTGTCAAACCCG 
                 279 
               
               
                   
               
               
                 1495878 
                 15284 
                 15299 
                 CTAGATAAACGCACTA 
                 280 
               
               
                   
               
               
                 1495912 
                 17181 
                 17196 
                 CACTACGACAGATGTC 
                 281 
               
               
                   
               
               
                 1495937 
                 2379 
                 2394 
                 ATACGAGGGCAATTCA 
                 282 
               
               
                   
               
               
                 1495941 
                 2383 
                 2398 
                 GAACATACGAGGGCAA 
                 283 
               
               
                   
               
               
                 1495952 
                 29634 
                 29649 
                 CGAAAGGTAAGATGGA 
                 284 
               
               
                   
               
               
                 1495970 
                 4785 
                 4800 
                 AAGAAATTGACCGCCT 
                 285 
               
               
                   
               
               
                 1495983 
                 711 
                 726 
                 CGCAAATTGCACAATT 
                 286 
               
               
                   
               
               
                 1495984 
                 712 
                 727 
                 CCGCAAATTGCACAAT 
                 287 
               
               
                   
               
               
                 1495995 
                 102 
                 117 
                 CCTATATGGAAGAGCC 
                 288 
               
               
                   
               
               
                 1495793 
                 1114 
                 1129 
                 CCAAAAGGCTTCTACG 
                 289 
               
               
                   
               
               
                 1495846 
                 14707 
                 14722 
                 CCACTAGAGGAGCTAC 
                 290 
               
               
                   
               
               
                 1495853 
                 14798 
                 14813 
                 AAGAATAGAGCTCGCA 
                 291 
               
               
                   
               
               
                 1495889 
                 16117 
                 16132 
                 TACCACATATATCACG 
                 292 
               
               
                   
               
               
                 1495948 
                 29599 
                 29614 
                 AACGAGAAAACACACG 
                 293 
               
               
                   
               
               
                 1495845 
                 14706 
                 14721 
                 CACTAGAGGAGCTACT 
                 294 
               
               
                   
               
               
                 1495964 
                 3611 
                 3626 
                 TTAATAGTTAATAGCG 
                 295 
               
               
                   
               
               
                 1495987 
                 724 
                 739 
                 TACAAACATTGGCCGC 
                 296 
               
               
                   
               
               
                 1495994 
                 101 
                 116 
                 CTATATGGAAGAGCCC 
                 297 
               
               
                   
               
               
                 1496005 
                 9111 
                 9126 
                 AATGATGAATGTCGCA 
                 298 
               
               
                   
               
               
                 1496006 
                 9112 
                 9127 
                 TAATGATGAATGTCGC 
                 299 
               
               
                   
               
               
                 1495848 
                 1491 
                 1506 
                 CCCAAGGTTTACCCAA 
                 300 
               
               
                   
               
               
                 1495854 
                 14799 
                 14814 
                 AAAGAATAGAGCTCGC 
                 301 
               
               
                   
               
               
                 1495865 
                 14879 
                 14894 
                 CAAGATGCACTTTTCG 
                 302 
               
               
                   
               
               
                 1495883 
                 15476 
                 15491 
                 AGTTTTGGACCACTAG 
                 303 
               
               
                   
               
               
                 1495930 
                 23425 
                 23440 
                 AAAACTACCGAAGTTG 
                 304 
               
               
                   
               
               
                 1495944 
                 276 
                 291 
                 GCAGAATGAATTCTCG 
                 305 
               
               
                   
               
               
                 1495956 
                 3303 
                 3318 
                 CTAGTAATAGGTTTCC 
                 306 
               
               
                   
               
               
                 1495972 
                 4787 
                 4802 
                 AAAAGAAATTGACCGC 
                 307 
               
               
                   
               
               
                 1495862 
                 14823 
                 14838 
                 GAATCTTAAGTATGCC 
                 308 
               
               
                   
               
               
                 1495872 
                 15217 
                 15232 
                 AACCCGGTAATTTTAA 
                 309 
               
               
                   
               
               
                 1495884 
                 15480 
                 15495 
                 TACAAGTTTTGGACCA 
                 310 
               
               
                   
               
               
                 1495911 
                 17045 
                 17060 
                 GGCTAGATTCCCTAAG 
                 311 
               
               
                   
               
               
                 1495933 
                 23428 
                 23443 
                 GTGAAAACTACCGAAG 
                 312 
               
               
                   
               
               
                 1495979 
                 544 
                 559 
                 GACGCATACAAAACAT 
                 313 
               
               
                   
               
               
                 1496004 
                 9092 
                 9107 
                 TATACTCAACTGTGTC 
                 314 
               
               
                   
               
               
                 1495830 
                 14038 
                 14053 
                 ACCTTACTAAAGGACC 
                 315 
               
               
                   
               
               
                 1495831 
                 14039 
                 14054 
                 GACCTTACTAAAGGAC 
                 316 
               
               
                   
               
               
                 1495844 
                 1485 
                 1500 
                 GTTTACCCAATAATAC 
                 317 
               
               
                   
               
               
                 1495893 
                 16374 
                 16389 
                 CACTAGTACTGATGTC 
                 318 
               
               
                   
               
               
                 1495946 
                 29253 
                 29268 
                 GTAAGAACGGTAATAA 
                 319 
               
               
                   
               
               
                 1495992 
                 99 
                 114 
                 ATATGGAAGAGCCCTA 
                 320 
               
               
                   
               
               
                 1495790 
                 10420 
                 10435 
                 GCAATTTAGGTGGTGC 
                 321 
               
               
                   
               
               
                 1495822 
                 13831 
                 13846 
                 CTAATCAGGAGTATGC 
                 322 
               
               
                   
               
               
                 1495873 
                 15218 
                 15233 
                 AAACCCGGTAATTTTA 
                 323 
               
               
                   
               
               
                 1495885 
                 15481 
                 15496 
                 CTACAAGTTTTGGACC 
                 324 
               
               
                   
               
               
                 1495888 
                 1610 
                 1625 
                 TGATAATGGACCCCAA 
                 325 
               
               
                   
               
               
                 1495900 
                 16430 
                 16445 
                 
                   GTTTTTAAACGGGTTT 
                 
                 326 
               
               
                   
               
               
                 1495929 
                 23424 
                 23439 
                 AAACTACCGAAGTTGT 
                 327 
               
               
                   
               
               
                 1495963 
                 3556 
                 3571 
                 CACTAGCCATCCTTAC 
                 328 
               
               
                   
               
               
                 1495985 
                 721 
                 736 
                 AAACATTGGCCGCAAA 
                 329 
               
               
                   
               
               
                 1496002 
                 9007 
                 9022 
                 ATAAAGGAGTTGCACC 
                 330 
               
               
                   
               
               
                 1496012 
                 9430 
                 9445 
                 TAACAGATGCGCAAAC 
                 331 
               
               
                   
               
               
                 1495802 
                 1215 
                 1230 
                 CAACTGAGGGAGCCTT 
                 332 
               
               
                   
               
               
                 1495965 
                 3613 
                 3628 
                 CGTTAATAGTTAATAG 
                 333 
               
               
                   
               
               
                 1496003 
                 9008 
                 9023 
                 GATAAAGGAGTTGCAC 
                 334 
               
               
                   
               
               
                 1496007 
                 9113 
                 9128 
                 ATAATGATGAATGTCG 
                 335 
               
               
                   
               
               
                 1496013 
                 9431 
                 9446 
                 ATAACAGATGCGCAAA 
                 336 
               
               
                   
               
               
                 1495804 
                 12794 
                 12809 
                 GGTAAGAGTCATTTTG 
                 337 
               
               
                   
               
               
                 1495821 
                 13830 
                 13845 
                 TAATCAGGAGTATGCT 
                 338 
               
               
                   
               
               
                 1495823 
                 13832 
                 13847 
                 CCTAATCAGGAGTATG 
                 339 
               
               
                   
               
               
                 1495828 
                 14036 
                 14051 
                 CTTACTAAAGGACCTC 
                 340 
               
               
                   
               
               
                 1495829 
                 14037 
                 14052 
                 CCTTACTAAAGGACCT 
                 341 
               
               
                   
               
               
                 1495867 
                 14916 
                 14931 
                 GGCTAGACTTTATTAT 
                 342 
               
               
                   
               
               
                 1495869 
                 14921 
                 14936 
                 GGTAAGGCTAGACTTT 
                 343 
               
               
                   
               
               
                 1495906 
                 16916 
                 16931 
                 CCTAAATAGAGGTATG 
                 344 
               
               
                   
               
               
                 1495920 
                 18450 
                 18465 
                 ATGCTTTAGATCAAGC 
                 345 
               
               
                   
               
               
                 1495962 
                 3515 
                 3530 
                 TGCAATATTGTTAACG 
                 346 
               
               
                   
               
               
                 1495835 
                 14425 
                 14440 
                 TTAAACCAGGTGGAAC 
                 347 
               
               
                   
               
               
                 1495882 
                 15389 
                 15404 
                 GTACATAATCAGGATG 
                 348 
               
               
                   
               
               
                 1495902 
                 16499 
                 16514 
                 GTGGAAAGGTTATGGC 
                 349 
               
               
                   
               
               
                 1495917 
                 17719 
                 17734 
                 GCTAATGGTGATTCTG 
                 350 
               
               
                   
               
               
                 1495931 
                 23426 
                 23441 
                 GAAAACTACCGAAGTT 
                 351 
               
               
                   
               
               
                 1495945 
                 2724 
                 2739 
                 GACAATATTGCTTTGC 
                 352 
               
               
                   
               
               
                 1495817 
                 1371 
                 1386 
                 ACCAAATTGGCTACTA 
                 353 
               
               
                   
               
               
                 1495824 
                 13833 
                 13848 
                 TCCTAATCAGGAGTAT 
                 354 
               
               
                   
               
               
                 1495827 
                 14035 
                 14050 
                 TTACTAAAGGACCTCA 
                 355 
               
               
                   
               
               
                 1495832 
                 14056 
                 14071 
                 AATGTTGGACTGAGAC 
                 356 
               
               
                   
               
               
                 1495864 
                 14841 
                 14856 
                 CCCTACTATAACTCAA 
                 357 
               
               
                   
               
               
                 1495977 
                 542 
                 557 
                 CGCATACAAAACATTC 
                 358 
               
               
                   
               
               
                 1495993 
                 100 
                 115 
                 TATATGGAAGAGCCCT 
                 359 
               
               
                   
               
               
                 1496014 
                 9432 
                 9447 
                 CATAACAGATGCGCAA 
                 360 
               
               
                   
               
               
                 1495794 
                 1115 
                 1130 
                 GCCAAAAGGCTTCTAC 
                 361 
               
               
                   
               
               
                 1495825 
                 13834 
                 13849 
                 ATCCTAATCAGGAGTA 
                 362 
               
               
                   
               
               
                 1495843 
                 1482 
                 1497 
                 TACCCAATAATACTGC 
                 363 
               
               
                   
               
               
                 1495874 
                 15219 
                 15234 
                 CAAACCCGGTAATTTT 
                 364 
               
               
                   
               
               
                 1495881 
                 15375 
                 15390 
                 TGTAAACTTACATAGC 
                 365 
               
               
                   
               
               
                 1495890 
                 16120 
                 16135 
                 TGGTACCACATATATC 
                 366 
               
               
                   
               
               
                 1495910 
                 17037 
                 17052 
                 TCCCTAAGAGTGATGG 
                 367 
               
               
                   
               
               
                 1495925 
                 22356 
                 22371 
                 GTACAACTATTGTTAA 
                 368 
               
               
                   
               
               
                 1495997 
                 889 
                 904 
                 GGCCAAACTGTCACTA 
                 369 
               
               
                   
               
               
                 1495789 
                 10419 
                 10434 
                 CAATTTAGGTGGTGCT 
                 370 
               
               
                   
               
               
                 1495833 
                 14060 
                 14075 
                 GCAAAATGTTGGACTG 
                 371 
               
               
                   
               
               
                 1495886 
                 15482 
                 15497 
                 CCTACAAGTTTTGGAC 
                 372 
               
               
                   
               
               
                 1495891 
                 16216 
                 16231 
                 CTAACTACCAACATGA 
                 373 
               
               
                   
               
               
                 1495915 
                 193 
                 208 
                 CATTAGGGAGGACTTG 
                 374 
               
               
                   
               
               
                 1495918 
                 196 
                 211 
                 TAACATTAGGGAGGAC 
                 375 
               
               
                   
               
               
                 1495960 
                 3314 
                 3329 
                 AACAATGGAACCTAGT 
                 376 
               
               
                   
               
               
                 1495973 
                 4852 
                 4867 
                 CATACATCACCAGATG 
                 377 
               
               
                   
               
               
                 1495988 
                 725 
                 740 
                 TTACAAACATTGGCCG 
                 378 
               
               
                   
               
               
                 1496001 
                 9006 
                 9021 
                 TAAAGGAGTTGCACCA 
                 379 
               
               
                   
               
               
                 1495791 
                 10421 
                 10436 
                 TGCAATTTAGGTGGTG 
                 380 
               
               
                   
               
               
                 1495801 
                 11932 
                 11947 
                 GCATAATGTCTGATAG 
                 381 
               
               
                   
               
               
                 1495805 
                 12798 
                 12813 
                 TACTGGTAAGAGTCAT 
                 382 
               
               
                   
               
               
                 1495813 
                 13456 
                 13471 
                 GAGGTATGAGCTATTA 
                 383 
               
               
                   
               
               
                 1495837 
                 14427 
                 14442 
                 TGTTAAACCAGGTGGA 
                 384 
               
               
                   
               
               
                 1495887 
                 15484 
                 15499 
                 CACCTACAAGTTTTGG 
                 385 
               
               
                   
               
               
                 1495942 
                 24502 
                 24517 
                 GCTAACTTTTGTGCAC 
                 386 
               
               
                   
               
               
                 1495957 
                 3305 
                 3320 
                 ACCTAGTAATAGGTTT 
                 387 
               
               
                   
               
               
                 1495991 
                 97 
                 112 
                 ATGGAAGAGCCCTAAT 
                 388 
               
               
                   
               
               
                 1496000 
                 912 
                 927 
                 CTGGTAAAGGCCAACA 
                 389 
               
               
                   
               
               
                 1495819 
                 13826 
                 13841 
                 CAGGAGTATGCTGATG 
                 390 
               
               
                   
               
               
                 1495820 
                 13829 
                 13844 
                 AATCAGGAGTATGCTG 
                 391 
               
               
                   
               
               
                 1495826 
                 14003 
                 14018 
                 CATACAATGCTAGTTA 
                 392 
               
               
                   
               
               
                 1495841 
                 14434 
                 14449 
                 CACTATATGTTAAACC 
                 393 
               
               
                   
               
               
                 1495856 
                 14801 
                 14816 
                 GCAAAGAATAGAGCTC 
                 394 
               
               
                   
               
               
                 1495892 
                 16217 
                 16232 
                 TCTAACTACCAACATG 
                 395 
               
               
                   
               
               
                 1495905 
                 16915 
                 16930 
                 CTAAATAGAGGTATGG 
                 396 
               
               
                   
               
               
                 1495908 
                 16920 
                 16935 
                 ACAACCTAAATAGAGG 
                 397 
               
               
                   
               
               
                 1495922 
                 19150 
                 19165 
                 GACTTTAACCTTGTGG 
                 398 
               
               
                   
               
               
                 1495958 
                 3306 
                 3321 
                 AACCTAGTAATAGGTT 
                 399 
               
               
                   
               
               
                 1495959 
                 3307 
                 3322 
                 GAACCTAGTAATAGGT 
                 400 
               
               
                   
               
               
                 1496009 
                 942 
                 957 
                 ACAGATTGAACCAGCT 
                 401 
               
               
                   
               
               
                 1495787 
                 10417 
                 10432 
                 ATTTAGGTGGTGCTGT 
                 402 
               
               
                   
               
               
                 1495834 
                 14387 
                 14402 
                 GCTTATGCTAATAGTG 
                 403 
               
               
                   
               
               
                 1495849 
                 1492 
                 1507 
                 CCCCAAGGTTTACCCA 
                 404 
               
               
                   
               
               
                 1495907 
                 16919 
                 16934 
                 CAACCTAAATAGAGGT 
                 405 
               
               
                   
               
               
                 1495932 
                 23427 
                 23442 
                 TGAAAACTACCGAAGT 
                 406 
               
               
                   
               
               
                 1495953 
                 3300 
                 3315 
                 GTAATAGGTTTCCTAT 
                 407 
               
               
                   
               
               
                 1495980 
                 5439 
                 5454 
                 TTAAACAACTTAGCTC 
                 408 
               
               
                   
               
               
                 1495999 
                 911 
                 926 
                 TGGTAAAGGCCAACAA 
                 409 
               
               
                   
               
               
                 1495786 
                 10109 
                 10124 
                 GCATTTGAGCTTTGGG 
                 410 
               
               
                   
               
               
                 1495836 
                 14426 
                 14441 
                 GTTAAACCAGGTGGAA 
                 411 
               
               
                   
               
               
                 1495879 
                 15373 
                 15388 
                 TAAACTTACATAGCTC 
                 412 
               
               
                   
               
               
                 1495880 
                 15374 
                 15389 
                 GTAAACTTACATAGCT 
                 413 
               
               
                   
               
               
                 1495923 
                 19483 
                 19498 
                 TACAATGGTTCACCAT 
                 414 
               
               
                   
               
               
                 1495954 
                 3301 
                 3316 
                 AGTAATAGGTTTCCTA 
                 415 
               
               
                   
               
               
                 1495955 
                 3302 
                 3317 
                 TAGTAATAGGTTTCCT 
                 416 
               
               
                   
               
               
                 1495961 
                 3315 
                 3330 
                 GAACAATGGAACCTAG 
                 417 
               
               
                   
               
               
                 1495974 
                 4855 
                 4870 
                 AATCATACATCACCAG 
                 418 
               
               
                   
               
               
                 1495800 
                 11931 
                 11946 
                 CATAATGTCTGATAGA 
                 419 
               
               
                   
               
               
                 1495809 
                 13043 
                 13058 
                 GACTATGGTGATGCTG 
                 420 
               
               
                   
               
               
                 1495838 
                 14430 
                 14445 
                 ATATGTTAAACCAGGT 
                 421 
               
               
                   
               
               
                 1495839 
                 14431 
                 14446 
                 TATATGTTAAACCAGG 
                 422 
               
               
                   
               
               
                 1495919 
                 197 
                 212 
                 GTAACATTAGGGAGGA 
                 423 
               
               
                   
               
               
                 1495978 
                 543 
                 558 
                 ACGCATACAAAACATT 
                 424 
               
               
                   
               
               
                 1495795 
                 1129 
                 1144 
                 CAAGGAACAACATTGC 
                 425 
               
               
                   
               
               
                 1495840 
                 14432 
                 14447 
                 CTATATGTTAAACCAG 
                 426 
               
               
                   
               
               
                 1495850 
                 14769 
                 14784 
                 CTCTATCTGTAGTACT 
                 427 
               
               
                   
               
               
                 1495857 
                 14803 
                 14818 
                 GTGCAAAGAATAGAGC 
                 428 
               
               
                   
               
               
                 1495860 
                 14821 
                 14836 
                 ATCTTAAGTATGCCAT 
                 429 
               
               
                   
               
               
                 1495863 
                 14840 
                 14855 
                 CCTACTATAACTCAAA 
                 430 
               
               
                   
               
               
                 1495870 
                 15066 
                 15081 
                 AACAATGTGTGATATC 
                 431 
               
               
                   
               
               
                 1495916 
                 17718 
                 17733 
                 CTAATGGTGATTCTGA 
                 432 
               
               
                   
               
               
                 1495924 
                 22353 
                 22368 
                 CAACTATTGTTAATGG 
                 433 
               
               
                   
               
               
                 1495976 
                 5224 
                 5239 
                 GGACAATCAAAAAGAG 
                 434 
               
               
                   
               
               
                 1495989 
                 89 
                 104 
                 GCCCTAATGTGTAAAA 
                 435 
               
               
                   
               
               
                 1495785 
                 10057 
                 10072 
                 TACTCAATAATTTGGG 
                 436 
               
               
                   
               
               
                 1495807 
                 12928 
                 12943 
                 CACAAGAGCACTATGT 
                 437 
               
               
                   
               
               
                 1495858 
                 14818 
                 14833 
                 TTAAGTATGCCATTAG 
                 438 
               
               
                   
               
               
                 1495859 
                 14819 
                 14834 
                 CTTAAGTATGCCATTA 
                 439 
               
               
                   
               
               
                 1495899 
                 16429 
                 16444 
                 TTTTTAAACGGGTTTG 
                 440 
               
               
                   
               
               
                 1495904 
                 16914 
                 16929 
                 TAAATAGAGGTATGGT 
                 441 
               
               
                   
               
               
                 1495909 
                 16921 
                 16936 
                 AACAACCTAAATAGAG 
                 442 
               
               
                   
               
               
                 1495935 
                 23470 
                 23485 
                 GTGGAAAATCCTACCA 
                 443 
               
               
                   
               
               
                 1495950 
                 29627 
                 29642 
                 TAAGATGGAGAGCCTT 
                 444 
               
               
                   
               
               
                 1495975 
                 525 
                 540 
                 CACCAACAGAGCCTAA 
                 445 
               
               
                   
               
               
                 1495784 
                 10056 
                 10071 
                 ACTCAATAATTTGGGT 
                 446 
               
               
                   
               
               
                 1495806 
                 12867 
                 12882 
                 TTCTAGCAATGTTGCA 
                 447 
               
               
                   
               
               
                 1495818 
                 13690 
                 13705 
                 TTTATGAGGCTATGTA 
                 448 
               
               
                   
               
               
                 1495868 
                 14919 
                 14934 
                 TAAGGCTAGACTTTAT 
                 449 
               
               
                   
               
               
                 1495981 
                 5440 
                 5455 
                 GTTAAACAACTTAGCT 
                 450 
               
               
                   
               
               
                 1496008 
                 9164 
                 9179 
                 GAAAAGTGTGACCTTC 
                 451 
               
               
                   
               
               
                 1495783 
                 117 
                 132 
                 TGCTAGGGAGAGCTGC 
                 452 
               
               
                   
               
               
                 1495799 
                 11791 
                 11806 
                 CTACACAGGCACCTAC 
                 453 
               
               
                   
               
               
                 1495803 
                 12406 
                 12421 
                 CACTAGAACCAGAATA 
                 454 
               
               
                   
               
               
                 1495808 
                 12929 
                 12944 
                 CCACAAGAGCACTATG 
                 455 
               
               
                   
               
               
                 1495943 
                 24504 
                 24519 
                 CTGCTAACTTTTGTGC 
                 456 
               
               
                   
               
               
                 1495951 
                 29630 
                 29645 
                 AGGTAAGATGGAGAGC 
                 457 
               
               
                   
               
               
                 1495990 
                 783 
                 798 
                 GTCCAGAACAAACCCA 
                 458 
               
               
                   
               
               
                 1495861 
                 14822 
                 14837 
                 AATCTTAAGTATGCCA 
                 459 
               
               
                   
               
               
                 1495871 
                 15068 
                 15083 
                 CCAACAATGTGTGATA 
                 460 
               
               
                   
               
               
                 1495903 
                 183 
                 198 
                 GACTTGAAAGAGCCAC 
                 461 
               
               
                   
               
               
                 1495921 
                 18456 
                 18471 
                 ATGGTAATGCTTTAGA 
                 462 
               
               
                   
               
               
                 1495934 
                 23468 
                 23483 
                 GGAAAATCCTACCATA 
                 463 
               
               
                   
               
               
                 1495949 
                 29600 
                 29615 
                 CAACGAGAAAACACAC 
                 464 
               
               
                   
               
               
                 1495966 
                 4084 
                 4099 
                 CATTACTTTATGATGC 
                 465 
               
               
                   
               
               
                 1495998 
                 896 
                 911 
                 ACAACAAGGCCAAACT 
                 466 
               
               
                   
               
               
                 1495788 
                 10418 
                 10433 
                 AATTTAGGTGGTGCTG 
                 467 
               
               
                   
               
               
                 1495866 
                 14882 
                 14897 
                 GATCAAGATGCACTTT 
                 468 
               
               
                   
               
               
                 1495914 
                 17484 
                 17499 
                 ACATTATCAACAATGC 
                 469 
               
               
                   
               
               
                 1495982 
                 5582 
                 5597 
                 TCTCTATGAGAACCAA 
                 470 
               
               
                   
               
            
           
         
       
     
     Modified oligonucleotides were designed as indicated in the tables below. The modified oligonucleotides are all uniform MOEs (i.e., every sugar moiety in the modified oligonucleotide is a 2′-MOE modified ribosyl sugar) of 18 or 20 nucleosides in length. The internucleoside linkages throughout each modified oligonucleotide are phosphorothioate linkages. All cytosine nucleobases throughout each modified oligonucleotide are 5-methylcytosines. 
     “Start site” indicates the 5′-most nucleoside of the target sequence to which the modified oligonucleotide is complementary. “Stop site” indicates the 3′-most nucleoside of the target sequence to which the modified oligonucleotide is complementary. As shown in the tables below, the modified oligonucleotides are 100% complementary to the genomic sequence of severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, designated herein as SEQ ID No:1 (GENBANK Accession No. NC_045512.2). 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Design of uniform MOE modified oligonucleotides 
               
               
                 complementary to severe acute respiratory 
               
               
                 syndrome coronavirus 2 isolate Wuhan-Hu-1 
               
            
           
           
               
               
               
               
               
            
               
                   
                 SEQ 
                 SEQ 
                   
                   
               
               
                   
                 ID 
                 ID 
                   
                   
               
               
                   
                 NO: 
                 NO: 
                   
                   
               
               
                   
                 1 
                 1 
                   
                 SEQ 
               
               
                 Compound 
                 Start 
                 Stop 
                 Sequence 
                 ID 
               
               
                 Number 
                 Site 
                 Site 
                 (5&#39; to 3&#39;) 
                 NO 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 1497428 
                 15 
                 32 
                 GTTTGTTACCTGGGAAGG 
                 471 
               
               
                   
               
               
                 1497429 
                 16 
                 33 
                 GGTTTGTTACCTGGGAAG 
                 472 
               
               
                   
               
               
                 1497430 
                 17 
                 34 
                 TGGTTTGTTACCTGGGAA 
                 473 
               
               
                   
               
               
                 1497431 
                 18 
                 35 
                 TTGGTTTGTTACCTGGGA 
                 474 
               
               
                   
               
               
                 1497432 
                 19 
                 36 
                 GTTGGTTTGTTACCTGGG 
                 475 
               
               
                   
               
               
                 1497433 
                 20 
                 37 
                 GGTTGGTTTGTTACCTGG 
                 476 
               
               
                   
               
               
                 1497434 
                 21 
                 38 
                 TGGTTGGTTTGTTACCTG 
                 477 
               
               
                   
               
               
                 1497435 
                 22 
                 39 
                 TTGGTTGGTTTGTTACCT 
                 478 
               
               
                   
               
               
                 1497436 
                 23 
                 40 
                 GTTGGTTGGTTTGTTACC 
                 479 
               
               
                   
               
               
                 1497437 
                 24 
                 41 
                 AGTTGGTTGGTTTGTTAC 
                 480 
               
               
                   
               
               
                 1497439 
                 25 
                 42 
                 AAGTTGGTTGGTTTGTTA 
                 481 
               
               
                   
               
               
                 1497440 
                 26 
                 43 
                 AAAGTTGGTTGGTTTGTT 
                 482 
               
               
                   
               
               
                 1497441 
                 27 
                 44 
                 GAAAGTTGGTTGGTTTGT 
                 483 
               
               
                   
               
               
                 1497442 
                 28 
                 45 
                 CGAAAGTTGGTTGGTTTG 
                 484 
               
               
                   
               
               
                 1497443 
                 29 
                 46 
                 TCGAAAGTTGGTTGGTTT 
                 485 
               
               
                   
               
               
                 1497444 
                 30 
                 47 
                 ATCGAAAGTTGGTTGGTT 
                 486 
               
               
                   
               
               
                 1497445 
                 31 
                 48 
                 GATCGAAAGTTGGTTGGT 
                 487 
               
               
                   
               
               
                 1497446 
                 32 
                 49 
                 AGATCGAAAGTTGGTTGG 
                 488 
               
               
                   
               
               
                 1497447 
                 33 
                 50 
                 GAGATCGAAAGTTGGTTG 
                 489 
               
               
                   
               
               
                 1497448 
                 34 
                 51 
                 AGAGATCGAAAGTTGGTT 
                 490 
               
               
                   
               
               
                 1497450 
                 35 
                 52 
                 AAGAGATCGAAAGTTGGT 
                 491 
               
               
                   
               
               
                 1497451 
                 36 
                 53 
                 CAAGAGATCGAAAGTTGG 
                 492 
               
               
                   
               
               
                 1497452 
                 37 
                 54 
                 ACAAGAGATCGAAAGTTG 
                 493 
               
               
                   
               
               
                 1497453 
                 38 
                 55 
                 TACAAGAGATCGAAAGTT 
                 494 
               
               
                   
               
               
                 1497454 
                 39 
                 56 
                 CTACAAGAGATCGAAAGT 
                 495 
               
               
                   
               
               
                 1497455 
                 40 
                 57 
                 TCTACAAGAGATCGAAAG 
                 496 
               
               
                   
               
               
                 1497456 
                 41 
                 58 
                 ATCTACAAGAGATCGAAA 
                 497 
               
               
                   
               
               
                 1497457 
                 42 
                 59 
                 GATCTACAAGAGATCGAA 
                 498 
               
               
                   
               
               
                 1497458 
                 43 
                 60 
                 AGATCTACAAGAGATCGA 
                 499 
               
               
                   
               
               
                 1497459 
                 44 
                 61 
                 CAGATCTACAAGAGATCG 
                 500 
               
               
                   
               
               
                 1497461 
                 45 
                 62 
                 ACAGATCTACAAGAGATC 
                 501 
               
               
                   
               
               
                 1497462 
                 46 
                 63 
                 AACAGATCTACAAGAGAT 
                 502 
               
               
                   
               
               
                 1497463 
                 47 
                 64 
                 GAACAGATCTACAAGAGA 
                 503 
               
               
                   
               
               
                 1497464 
                 48 
                 65 
                 AGAACAGATCTACAAGAG 
                 504 
               
               
                   
               
               
                 1497465 
                 49 
                 66 
                 GAGAACAGATCTACAAGA 
                 505 
               
               
                   
               
               
                 1497466 
                 50 
                 67 
                 AGAGAACAGATCTACAAG 
                 506 
               
               
                   
               
               
                 1497467 
                 51 
                 68 
                 TAGAGAACAGATCTACAA 
                 507 
               
               
                   
               
               
                 1497468 
                 52 
                 69 
                 TTAGAGAACAGATCTACA 
                 508 
               
               
                   
               
               
                 1497469 
                 53 
                 70 
                 TTTAGAGAACAGATCTAC 
                 509 
               
               
                   
               
               
                 1497492 
                 54 
                 71 
                 GTTTAGAGAACAGATCTA 
                 510 
               
               
                   
               
               
                 1497335 
                 15 
                 34 
                 TGGTTTGTTACCTGGGAAGG 
                 511 
               
               
                   
               
               
                 1497407 
                 16 
                 35 
                 TTGGTTTGTTACCTGGGAAG 
                 512 
               
               
                   
               
               
                 1497418 
                 17 
                 36 
                 GTTGGTTTGTTACCTGGGAA 
                 513 
               
               
                   
               
               
                 1497427 
                 18 
                 37 
                 GGTTGGTTTGTTACCTGGGA 
                 514 
               
               
                   
               
               
                 1497438 
                 19 
                 38 
                 TGGTTGGTTTGTTACCTGGG 
                 515 
               
               
                   
               
               
                 1497449 
                 20 
                 39 
                 TTGGTTGGTTTGTTACCTGG 
                 516 
               
               
                   
               
               
                 1497460 
                 21 
                 40 
                 GTTGGTTGGTTTGTTACCTG 
                 517 
               
               
                   
               
               
                 1497470 
                 22 
                 41 
                 AGTTGGTTGGTTTGTTACCT 
                 518 
               
               
                   
               
               
                 1497480 
                 23 
                 42 
                 AAGTTGGTTGGTTTGTTACC 
                 519 
               
               
                   
               
               
                 1497336 
                 24 
                 43 
                 AAAGTTGGTTGGTTTGTTAC 
                 520 
               
               
                   
               
               
                 1497347 
                 25 
                 44 
                 GAAAGTTGGTTGGTTTGTTA 
                 521 
               
               
                   
               
               
                 1497358 
                 26 
                 45 
                 CGAAAGTTGGTTGGTTTGTT 
                 522 
               
               
                   
               
               
                 1497366 
                 27 
                 46 
                 TCGAAAGTTGGTTGGTTTGT 
                 523 
               
               
                   
               
               
                 1497377 
                 28 
                 47 
                 ATCGAAAGTTGGTTGGTTTG 
                 524 
               
               
                   
               
               
                 1497388 
                 29 
                 48 
                 GATCGAAAGTTGGTTGGTTT 
                 525 
               
               
                   
               
               
                 1497399 
                 30 
                 49 
                 AGATCGAAAGTTGGTTGGTT 
                 526 
               
               
                   
               
               
                 1497404 
                 31 
                 50 
                 GAGATCGAAAGTTGGTTGGT 
                 527 
               
               
                   
               
               
                 1497405 
                 32 
                 51 
                 AGAGATCGAAAGTTGGTTGG 
                 528 
               
               
                   
               
               
                 1497406 
                 33 
                 52 
                 AAGAGATCGAAAGTTGGTTG 
                 529 
               
               
                   
               
               
                 1497408 
                 34 
                 53 
                 CAAGAGATCGAAAGTTGGTT 
                 530 
               
               
                   
               
               
                 1497409 
                 35 
                 54 
                 ACAAGAGATCGAAAGTTGGT 
                 531 
               
               
                   
               
               
                 1497410 
                 36 
                 55 
                 TACAAGAGATCGAAAGTTGG 
                 532 
               
               
                   
               
               
                 1497411 
                 37 
                 56 
                 CTACAAGAGATCGAAAGTTG 
                 533 
               
               
                   
               
               
                 1497412 
                 38 
                 57 
                 TCTACAAGAGATCGAAAGTT 
                 534 
               
               
                   
               
               
                 1497413 
                 39 
                 58 
                 ATCTACAAGAGATCGAAAGT 
                 535 
               
               
                   
               
               
                 1497414 
                 40 
                 59 
                 GATCTACAAGAGATCGAAAG 
                 536 
               
               
                   
               
               
                 1497415 
                 41 
                 60 
                 AGATCTACAAGAGATCGAAA 
                 537 
               
               
                   
               
               
                 1497416 
                 42 
                 61 
                 CAGATCTACAAGAGATCGAA 
                 538 
               
               
                   
               
               
                 348264 
                 43 
                 62 
                 ACAGATCTACAAGAGATCGA 
                 539 
               
               
                   
               
               
                 1497419 
                 44 
                 63 
                 AACAGATCTACAAGAGATCG 
                 540 
               
               
                   
               
               
                 348265 
                 45 
                 64 
                 GAACAGATCTACAAGAGATC 
                 541 
               
               
                   
               
               
                 1497421 
                 46 
                 65 
                 AGAACAGATCTACAAGAGAT 
                 542 
               
               
                   
               
               
                 348266 
                 47 
                 66 
                 GAGAACAGATCTACAAGAGA 
                 543 
               
               
                   
               
               
                 1497423 
                 48 
                 67 
                 AGAGAACAGATCTACAAGAG 
                 544 
               
               
                   
               
               
                 348267 
                 49 
                 68 
                 TAGAGAACAGATCTACAAGA 
                 545 
               
               
                   
               
               
                 1497425 
                 50 
                 69 
                 TTAGAGAACAGATCTACAAG 
                 546 
               
               
                   
               
               
                 348268 
                 51 
                 70 
                 TTTAGAGAACAGATCTACAA 
                 547 
               
               
                   
               
               
                 1497491 
                 52 
                 71 
                 GTTTAGAGAACAGATCTACA 
                 548 
               
               
                   
               
            
           
         
       
     
     Modified oligonucleotides were designed as indicated in the tables below. The modified oligonucleotides are 16 nucleosides in length. The chemistry notation column in the tables below specifies the specific chemistry notation for modified oligonucleotides; wherein subscript ‘d’ represents a 2′-β-D-deoxyribosyl sugar moiety, subscript ‘e’ represents a 2′-MOE sugar moiety, subscript ‘k’ represents a cEt modified sugar moiety, subscript ‘s’ represents a phosphorothioate internucleoside linkage, and superscript ‘m’ before the cytosine residue ( m C) represents a 5-methyl cytosine. The internucleoside linkages throughout each modified oligonucleotide are phosphorothioate linkages. All cytosine nucleobases throughout each modified oligonucleotide are 5-methylcytosines. 
     “Start site” indicates the 5′-most nucleoside of the target sequence to which the modified oligonucleotide is complementary. “Stop site” indicates the 3′-most nucleoside of the target sequence to which the modified oligonucleotide is complementary. As shown in the tables below, the modified oligonucleotides are 100% complementary to the genomic sequence of severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, designated herein as SEQ ID No:1 (GENBANK Accession No. NC_045512.2). 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Design of modified oligonucleotides complementary to severe 
               
               
                 acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 SEQ 
                 SEQ 
                   
                   
                 SEQ 
               
               
                   
                 ID 
                 ID 
                   
                   
                 ID 
               
               
                   
                 NO: 1 
                 NO: 1 
                   
                   
                 NO 
               
               
                 ION 
                 Start 
                 Stop 
                 Sequence 
                   
                   
               
               
                 Number 
                 site 
                 site 
                 (5&#39; to 3&#39;) 
                 Chemistry Notation (5&#39; to 3&#39;) 
               
               
                   
               
               
                 1497360 
                 15 
                 30 
                 TTGTTAC 
                 T ks T dS G ds T ks T dS A dS   m C ks   m C ds T dS G ks G ds G dS A kS A dS G ds G k   
                 549 
               
               
                   
                   
                   
                 CTGGGAA 
                   
                   
               
               
                   
                   
                   
                 GG 
                   
                   
               
               
                   
               
               
                 1497361 
                 16 
                 31 
                 TTTGTTA 
                 T ks T ds T ds G ks T ds T ds A ks   m C ds   m C ds T ks G ds G ds G ks A ds A ds G k   
                 550 
               
               
                   
                   
                   
                 CCTGGGA 
                   
                   
               
               
                   
                   
                   
                 AG 
                   
                   
               
               
                   
               
               
                 1497362 
                 17 
                 32 
                 GTTTGTT 
                 G ks T dS T dS T kS G ds T dS T kS A dS   m C ds   m C ks T dS G ds G ks G ds A dS A k   
                 551 
               
               
                   
                   
                   
                 ACCTGGG 
                   
                   
               
               
                   
                   
                   
                 AA 
                   
                   
               
               
                   
               
               
                 1497363 
                 18 
                 33 
                 GGTTTGT 
                 G ks G ds T dS T kS T dS G ds T kS T dS A ds   m C ks   m C ds T ds G ks G ds G ds A k   
                 552 
               
               
                   
                   
                   
                 TACCTGG 
                   
                   
               
               
                   
                   
                   
                 GA 
                   
                   
               
               
                   
               
               
                 1497364 
                 19 
                 34 
                 TGGTTTG 
                 T ks G ds G ds T ks T ds T ds G ks T ds T ds A ks   m C ds   m C ds T ks G ds G ds G k   
                 553 
               
               
                   
                   
                   
                 TTACCTG 
                   
                   
               
               
                   
                   
                   
                 GG 
                   
                   
               
               
                   
               
               
                 1497365 
                 20 
                 35 
                 TTGGTTT 
                 T ks T ds G ds G ks T ds T ds T ks G ds T ds T ks A ds   m C ds   m C ks T ds G ds G k   
                 554 
               
               
                   
                   
                   
                 GTTACCT 
                   
                   
               
               
                   
                   
                   
                 GG 
                   
                   
               
               
                   
               
               
                 1497367 
                 21 
                 36 
                 GTTGGTT 
                 G ks T ds T ds G ks G ds T ds T ks T ds G ds T ks T ds A ds   m C ks   m C ds T ds G k   
                 555 
               
               
                   
                   
                   
                 TGTTACC 
                   
                   
               
               
                   
                   
                   
                 TG 
                   
                   
               
               
                   
               
               
                 1497368 
                 22 
                 37 
                 GGTTGGT 
                 G ks G ds T ds T ks G ds G ds T ks T ds T ds G ks T ds T ds A ks   m   cds   m C ds T k   
                 556 
               
               
                   
                   
                   
                 TTGTTAC 
                   
                   
               
               
                   
                   
                   
                 CT 
                   
                   
               
               
                   
               
               
                 1497369 
                 23 
                 38 
                 TGGTTGG 
                 T ks G ds G ds T ks T ds G ds G ks T ds T ds T ks G ds T ds T ks A ds   m C ds   m C k   
                 557 
               
               
                   
                   
                   
                 TTTGTTA 
                   
                   
               
               
                   
                   
                   
                 CC 
                   
                   
               
               
                   
               
               
                 1497370 
                 24 
                 39 
                 TTGGTTG 
                 T ks T dS G ds G ks T dS T dS G ks G ds T dS T kS T dS G ds T ks T ds A ds   m C k   
                 558 
               
               
                   
                   
                   
                 GTTTGTT 
                   
                   
               
               
                   
                   
                   
                 AC 
                   
                   
               
               
                   
               
               
                 1497371 
                 25 
                 40 
                 GTTGGTT 
                 G ks T ds T ds G ks G ds T ds T ks G ds G ds T ks T ds T ds G ks T ds T ds A k   
                 559 
               
               
                   
                   
                   
                 GGTTTGT 
                   
                   
               
               
                   
                   
                   
                 TA 
                   
                   
               
               
                   
               
               
                 1497372 
                 26 
                 41 
                 AGTTGGT 
                 A ks G ds T ds T ks G ds G ds T ks T ds G ds G ks T ds T ds T ks G ds T ds T k   
                 560 
               
               
                   
                   
                   
                 TGGTTTG 
                   
                   
               
               
                   
                   
                   
                 TT 
                   
                   
               
               
                   
               
               
                 1497373 
                 27 
                 42 
                 AAGTTGG 
                 A ks A ds G ds T ks T ds G ds G ks T ds T ds G ks G ds T ds T ks T ds G ds T k   
                 561 
               
               
                   
                   
                   
                 TTGGTTT 
                   
                   
               
               
                   
                   
                   
                 GT 
                   
                   
               
               
                   
               
               
                 1497374 
                 28 
                 43 
                 AAAGTTG 
                 A ks A ds A ds G ks T ds T ds G ks G ds T ds T ks G ds G ds T ks T ds T ds G k   
                 562 
               
               
                   
                   
                   
                 GTTGGTT 
                   
                   
               
               
                   
                   
                   
                 TG 
                   
                   
               
               
                   
               
               
                 1497375 
                 29 
                 44 
                 GAAAGTT 
                 G ks A ds A ds A ks G ds T ds T ks G ds G ds T ks T ds G ds G ks T ds T ds T k   
                 563 
               
               
                   
                   
                   
                 GGTTGGT 
                   
                   
               
               
                   
                   
                   
                 TT 
                   
                   
               
               
                   
               
               
                 1497376 
                 30 
                 45 
                 CGAAAGT 
                   m C ks G ds A ds A ks A ds G ds T ks T ds G ds G ks T ds T ds G ks G ds T ds T k   
                 564 
               
               
                   
                   
                   
                 TGGTTGG 
                   
                   
               
               
                   
                   
                   
                 TT 
                   
                   
               
               
                   
               
               
                 1497378 
                 31 
                 46 
                 TCGAAAG 
                 T ks   m C ds G ds A kS A dS A dS G ks T dS T ds G ks G ds T ds T ks G ds G ds T k   
                 565 
               
               
                   
                   
                   
                 TTGGTTG 
                   
                   
               
               
                   
                   
                   
                 GT 
                   
                   
               
               
                   
               
               
                 1497379 
                 32 
                 47 
                 ATCGAAA 
                 A ks T ds   m C ds G ks A ds A ds A ks G ds T ds T ks G ds G ds T ks T ds G ds G k   
                 566 
               
               
                   
                   
                   
                 GTTGGTT 
                   
                   
               
               
                   
                   
                   
                 GG 
                   
                   
               
               
                   
               
               
                 1497380 
                 33 
                 48 
                 GATCGAA 
                 G ks A ds T ds   m C ks G ds A ds A ks A ds G ds T ks T ds G ds G ks T ds T ds G k   
                 567 
               
               
                   
                   
                   
                 AGTTGGT 
                   
                   
               
               
                   
                   
                   
                 TG 
                   
                   
               
               
                   
               
               
                 1497381 
                 34 
                 49 
                 AGATCGA 
                 A ks G ds A ds T ks C ds G ds A ks A ds A ds G ks T ds T ds G ks G ds T ds T k   
                 568 
               
               
                   
                   
                   
                 AAGTTGG 
                   
                   
               
               
                   
                   
                   
                 TT 
                   
                   
               
               
                   
               
               
                 1497382 
                 35 
                 50 
                 GAGATCG 
                 G ks A ds G ds A ks T ds C ds G ks A ds A ds A ks G ds T ds T ks G ds G ds T k   
                 569 
               
               
                   
                   
                   
                 AAAGTTG 
                   
                   
               
               
                   
                   
                   
                 GT 
                   
                   
               
               
                   
               
               
                 1497383 
                 36 
                 51 
                 AGAGATC 
                 A ks G ds A ds G ks A ds T ds C ks G ds A ds A ks A ds G ds T ks T ds G ds G k   
                 570 
               
               
                   
                   
                   
                 GAAAGTT 
                   
                   
               
               
                   
                   
                   
                 GG 
                   
                   
               
               
                   
               
               
                 1497384 
                 37 
                 52 
                 AAGAGAT 
                 A ks A ds G ds A ks G ds A ds T ks C ds G ds A ks A ds A ds G ks T ds T ds G k   
                 571 
               
               
                   
                   
                   
                 CGAAAGT 
                   
                   
               
               
                   
                   
                   
                 TG 
                   
                   
               
               
                   
               
               
                 1497385 
                 38 
                 53 
                 CAAGAG 
                 C ks A ds A ds G ks A ds G ds A ks T ds C ds G ks A ds A ds A ks G ds T ds T k   
                 572 
               
               
                   
                   
                   
                 ATCGAAA 
                   
                   
               
               
                   
                   
                   
                 GTT 
                   
                   
               
               
                   
               
               
                 1497386 
                 39 
                 54 
                 ACAAGA 
                 A ks C ds A ds A ks G ds A ds G ks A ds T ds C ks G ds A ds A ks A ds G ds T k   
                 573 
               
               
                   
                   
                   
                 GATCGAA 
                   
                   
               
               
                   
                   
                   
                 AGT 
                   
                   
               
               
                   
               
               
                 1497387 
                 40 
                 55 
                 TACAAGA 
                 T ks A ds C ds A ks A ds G ds A ks G ds A ds T ks C ds G ds A ks A ds A ds G k   
                 574 
               
               
                   
                   
                   
                 GATCGAA 
                   
                   
               
               
                   
                   
                   
                 AG 
                   
                   
               
               
                   
               
               
                 1497389 
                 41 
                 56 
                 CTACAAG 
                 C ks T as A as C ks A ds A ds G ks A ds G ds A ks T ds C as G s A as A as A k   
                 575 
               
               
                   
                   
                   
                 AGATCGA 
                   
                   
               
               
                   
                   
                   
                 AA 
                   
                   
               
               
                   
               
               
                 1497390 
                 42 
                 57 
                 TCTACAA 
                 T ks   m C ds T ds A kS   m C ds A dS A ks G ds A dS G ks A dS T dS   m C ks G ds A dS A k   
                 576 
               
               
                   
                   
                   
                 GAGATCG 
                   
                   
               
               
                   
                   
                   
                 AA 
                   
                   
               
               
                   
               
               
                 1497391 
                 43 
                 58 
                 ATCTACA 
                 A ks T ds   m C ds T ks A ds   m C ds A ks A ds G ds A ks G ds A ds T ks   m C ds G ds A k   
                 577 
               
               
                   
                   
                   
                 AGAGATC 
                   
                   
               
               
                   
                   
                   
                 GA 
                   
                   
               
               
                   
               
               
                 1497392 
                 44 
                 59 
                 GATCTAC 
                 G ks A ds T ds   m C ks T ds A ds   m C ks A ds A ds G ks A ds G ds A ks T ds   m C ds G k   
                 578 
               
               
                   
                   
                   
                 AAGAGAT 
                   
                   
               
               
                   
                   
                   
                 CG 
                   
                   
               
               
                   
               
               
                 1497393 
                 45 
                 60 
                 AGATCTA 
                 A kS G ds A dS T kS   m C ds T ds A kS   m C ds A dS A ks G ds A dS G ks A dS T dS   m C k   
                 579 
               
               
                   
                   
                   
                 CAAGAG 
                   
                   
               
               
                   
                   
                   
                 ATC 
                   
                   
               
               
                   
               
               
                 1497394 
                 46 
                 61 
                 CAGATCT 
                   m C ks A ds G ds A ks T ds   m C ds T ks A ds   m C ds A ks A ds G ds A ks G ds A ds T k   
                 580 
               
               
                   
                   
                   
                 ACAAGA 
                   
                   
               
               
                   
                   
                   
                 GAT 
                   
                   
               
               
                   
               
               
                 1497395 
                 47 
                 62 
                 ACAGATC 
                 A ks C ds A ds G ks A ds T ds C ks T as A ds C ks A as A as G ks A a G a A k   
                 581 
               
               
                   
                   
                   
                 TACAAGA 
                   
                   
               
               
                   
                   
                   
                 GA 
                   
                   
               
               
                   
               
               
                 1497396 
                 48 
                 63 
                 AACAGAT 
                 A ks A ds C as A k G as A as T ks C as T ds A ks C ds A ds A ks G ds A ds G k   
                 582 
               
               
                   
                   
                   
                 CTACAAG 
                   
                   
               
               
                   
                   
                   
                 AG 
                   
                   
               
               
                   
               
               
                 1497397 
                 49 
                 64 
                 GAACAG 
                 G ks A ds A ds C s A as G as A ks T as C ds T ks A ds C as A ks A a G as A k   
                 583 
               
               
                   
                   
                   
                 ATCTACA 
                   
                   
               
               
                   
                   
                   
                 AGA 
                   
                   
               
               
                   
               
               
                 1497398 
                 50 
                 65 
                 AGAACA 
                 A ks G ds A ds A ks C ds A ds G ks A ds T ds C ks T as A ds C ks A ds A ds G k   
                 584 
               
               
                   
                   
                   
                 GATCTAC 
                   
                   
               
               
                   
                   
                   
                 AAG 
                   
                   
               
               
                   
               
               
                 1497400 
                 51 
                 66 
                 GAGAAC 
                 G ks A ds G ds A ks A ds C as A k G as A as T ks C as T as A ks C as A a A k   
                 585 
               
               
                   
                   
                   
                 AGATCTA 
                   
                   
               
               
                   
                   
                   
                 CAA 
                   
                   
               
               
                   
               
               
                 1497401 
                 52 
                 67 
                 AGAGAA 
                 A ks G ds A ds G ks A ds A ds C ks A ds G ds A ks T ds C ds T ks A ds C a A k   
                 586 
               
               
                   
                   
                   
                 CAGATCT 
                   
                   
               
               
                   
                   
                   
                 ACA 
                   
                   
               
               
                   
               
               
                 1497402 
                 53 
                 68 
                 TAGAGAA 
                 T ks A ds G ds A ks G ds A ds A ks   m C ds A ds G ks A ds T ds   m C ks T ds A ds   m C k   
                 587 
               
               
                   
                   
                   
                 CAGATCT 
                   
                   
               
               
                   
                   
                   
                 AC 
                   
                   
               
               
                   
               
               
                 1497471 
                 15 
                 30 
                 TTGTTAC 
                 T ks T es G es T ks T es A es   m C ks   m C es T es G ks G es G es A ks A es G es G k   
                 549 
               
               
                   
                   
                   
                 CTGGGAA 
                   
                   
               
               
                   
                   
                   
                 GG 
                   
                   
               
               
                   
               
               
                 1497472 
                 16 
                 31 
                 TTTGTTA 
                 T ks T es T es G ks T es T es A ks   m C es   m C es T ks G es G es G ks A es A es G k   
                 550 
               
               
                   
                   
                   
                 CCTGGGA 
                   
                   
               
               
                   
                   
                   
                 AG 
                   
                   
               
               
                   
               
               
                 1497473 
                 17 
                 32 
                 GTTTGTT 
                 G ks T es T es T ks G es T es T ks A es   m C es   m C ks T es G es G ks G es A es A k   
                 551 
               
               
                   
                   
                   
                 ACCTGGG 
                   
                   
               
               
                   
                   
                   
                 AA 
                   
                   
               
               
                   
               
               
                 1497474 
                 18 
                 33 
                 GGTTTGT 
                 G ks G es T es T ks T es G es T ks T es A es   m C ks   m C es T es G ks G es G es A k   
                 552 
               
               
                   
                   
                   
                 TACCTGG 
                   
                   
               
               
                   
                   
                   
                 GA 
                   
                   
               
               
                   
               
               
                 1497475 
                 19 
                 34 
                 TGGTTTG 
                 T ks G es G es T ks T es T es G ks T es T es A ks C es C es T ks G es G es G k   
                 553 
               
               
                   
                   
                   
                 TTACCTG 
                   
                   
               
               
                   
                   
                   
                 GG 
                   
                   
               
               
                   
               
               
                 1497476 
                 20 
                 35 
                 TTGGTTT 
                 T ks G es G es T ks T es T es G ks T es T es A ks   m C es   m C es T ks G es G es G k   
                 554 
               
               
                   
                   
                   
                 GTTACCT 
                   
                   
               
               
                   
                   
                   
                 GG 
                   
                   
               
               
                   
               
               
                 1497477 
                 21 
                 36 
                 GTTGGTT 
                 G ks T es T es G ks G es T es T ks T es G es T ks T es A es   m C ks   m C es T es G k   
                 555 
               
               
                   
                   
                   
                 TGTTACC 
                   
                   
               
               
                   
                   
                   
                 TG 
                   
                   
               
               
                   
               
               
                 1497478 
                 22 
                 37 
                 GGTTGGT 
                 G ks G es T es T ks G es G es T ks T es T es G ks T es T es A ks   m C es   m C es T k   
                 556 
               
               
                   
                   
                   
                 TTGTTAC 
                   
                   
               
               
                   
                   
                   
                 CT 
                   
                   
               
               
                   
               
               
                 1497479 
                 23 
                 38 
                 TGGTTGG 
                 T ks G es G es T ks T es G es G ks T es T es T ks G es T es T ks A es   m C es   m C k   
                 557 
               
               
                   
                   
                   
                 TTTGTTA 
                   
                   
               
               
                   
                   
                   
                 CC 
                   
                   
               
               
                   
               
               
                 1497481 
                 24 
                 39 
                 TTGGTTG 
                 T ks T es G es G ks T es T es G ks G es T es T ks T es G es T ks T es A es   m C k   
                 558 
               
               
                   
                   
                   
                 GTTTGTT 
                   
                   
               
               
                   
                   
                   
                 AC 
                   
                   
               
               
                   
               
               
                 1497482 
                 25 
                 40 
                 GTTGGTT 
                 G ks T es T es G ks G es T es T ks G es G es T ks T es T es G ks T es T es A k   
                 559 
               
               
                   
                   
                   
                 GGTTTGT 
                   
                   
               
               
                   
                   
                   
                 TA 
                   
                   
               
               
                   
               
               
                 1497483 
                 26 
                 41 
                 AGTTGGT 
                 A ks G es T es T ks G es G es T ks T es G es G ks T es T es T ks G es T es T k   
                 560 
               
               
                   
                   
                   
                 TGGTTTG 
                   
                   
               
               
                   
                   
                   
                 TT 
                   
                   
               
               
                   
               
               
                 1497484 
                 27 
                 42 
                 AAGTTGG 
                 A ks A es G es T ks T es G es G ks T es T es G ks G es T es T ks T es G es T k   
                 561 
               
               
                   
                   
                   
                 TTGGTTT 
                   
                   
               
               
                   
                   
                   
                 GT 
                   
                   
               
               
                   
               
               
                 1497485 
                 28 
                 43 
                 AAAGTTG 
                 A ks A es A es G ks T es T es G ks G es T es T ks G es G es T ks T es T es G k   
                 562 
               
               
                   
                   
                   
                 GTTGGTT 
                   
                   
               
               
                   
                   
                   
                 TG 
                   
                   
               
               
                   
               
               
                 1497486 
                 29 
                 44 
                 GAAAGTT 
                 G ks A es A es A ks G es T es T ks G es G es T ks T es G es G ks T es T es T k   
                 563 
               
               
                   
                   
                   
                 GGTTGGT 
                   
                   
               
               
                   
                   
                   
                 TT 
                   
                   
               
               
                   
               
               
                 1497487 
                 30 
                 45 
                 CGAAAGT 
                   m C ks G es A es A ks A es G es T ks T es G es G ks T es T es G ks G es T es T k   
                 564 
               
               
                   
                   
                   
                 TGGTTGG 
                   
                   
               
               
                   
                   
                   
                 TT 
                   
                   
               
               
                   
               
               
                 1497488 
                 31 
                 46 
                 TCGAAAG 
                 T ks   m C es G es A ks A es A es G ks T es T es G ks G es T es T ks G es G es T k   
                 565 
               
               
                   
                   
                   
                 TTGGTTG 
                   
                   
               
               
                   
                   
                   
                 GT 
                   
                   
               
               
                   
               
               
                 1497489 
                 32 
                 47 
                 ATCGAAA 
                 A ks T eS   m C eS G ks A eS A eS A ks G eS T eS T ks G eS G eS T ks T es G eS G k   
                 566 
               
               
                   
                   
                   
                 GTTGGTT 
                   
                   
               
               
                   
                   
                   
                 GG 
                   
                   
               
               
                   
               
               
                 1497490 
                 33 
                 48 
                 GATCGAA 
                 G ks A es T es   m C ks G es A es A ks A es G es T ks T es G es G ks T es T es G k   
                 567 
               
               
                   
                   
                   
                 AGTTGGT 
                   
                   
               
               
                   
                   
                   
                 TG 
                   
                   
               
               
                   
               
               
                 1497337 
                 34 
                 49 
                 AGATCGA 
                 A k G es A es T ks C es G es A ks A es A es G ks T es T es G ks G es T es T k   
                 568 
               
               
                   
                   
                   
                 AAGTTGG 
                   
                   
               
               
                   
                   
                   
                 TT 
                   
                   
               
               
                   
               
               
                 1497338 
                 35 
                 50 
                 GAGATCG 
                 G ks A es G es A ks T es   m C es G ks A es A es A ks G es T es T ks G e G es T k   
                 569 
               
               
                   
                   
                   
                 AAAGTTG 
                   
                   
               
               
                   
                   
                   
                 GT 
                   
                   
               
               
                   
               
               
                 1497339 
                 36 
                 51 
                 AGAGATC 
                 A ks G es A es G ks A es T es C ks G es A es A ks A es G es T ks T es G es G k   
                 570 
               
               
                   
                   
                   
                 GAAAGTT 
                   
                   
               
               
                   
                   
                   
                 GG 
                   
                   
               
               
                   
               
               
                 1497340 
                 37 
                 52 
                 AAGAGAT 
                 A ks A es G es A ks G es A es T ks C es G es A ks A es A es G ks T es T es G k   
                 571 
               
               
                   
                   
                   
                 CGAAAGT 
                   
                   
               
               
                   
                   
                   
                 TG 
                   
                   
               
               
                   
               
               
                 1497341 
                 38 
                 53 
                 CAAGAG 
                   m C ks A es A es G ks A es G es A ks T es   m C es G ks A es A es A ks G es T es T k   
                 572 
               
               
                   
                   
                   
                 ATCGAAA 
                   
                   
               
               
                   
                   
                   
                 GTT 
                   
                   
               
               
                   
               
               
                 1497342 
                 39 
                 54 
                 ACAAGA 
                 A ks   m C es A es A ks G es A es G ks A es T es   m C ks G es A es A ks A es G es T k   
                 573 
               
               
                   
                   
                   
                 GATCGAA 
                   
                   
               
               
                   
                   
                   
                 AGT 
                   
                   
               
               
                   
               
               
                 1497343 
                 40 
                 55 
                 TACAAGA 
                 T ks A es   m C es A ks A es G es A ks G es A es T ks   m C es G es A ks A es A es G k   
                 574 
               
               
                   
                   
                   
                 GATCGAA 
                   
                   
               
               
                   
                   
                   
                 AG 
                   
                   
               
               
                   
               
               
                 1497344 
                 41 
                 56 
                 CTACAAG 
                   m C ks T es A es   m C ks A es A es G ks A es G es A ks T es   m C es G ks A es A es A k   
                 575 
               
               
                   
                   
                   
                 AGATCGA 
                   
                   
               
               
                   
                   
                   
                 AA 
                   
                   
               
               
                   
               
               
                 1497345 
                 42 
                 57 
                 TCTACAA 
                 T ks   m C es T es A ks   m C es A es A ks G es A es G ks A es T es   m C ks G es A es A k   
                 576 
               
               
                   
                   
                   
                 GAGATCG 
                   
                   
               
               
                   
                   
                   
                 AA 
                   
                   
               
               
                   
               
               
                 1497346 
                 43 
                 58 
                 ATCTACA 
                 A ks T es   m C es T ks A es   m C es A ks A es G es A ks G es A es T ks   m C es G es A k   
                 577 
               
               
                   
                   
                   
                 AGAGATC 
                   
                   
               
               
                   
                   
                   
                 GA 
                   
                   
               
               
                   
               
               
                 1497348 
                 44 
                 59 
                 GATCTAC 
                 G ks A es T es   m C ks T es A es   m C ks A es A es G ks A es G es A ks T es   m C es G k   
                 578 
               
               
                   
                   
                   
                 AAGAGAT 
                   
                   
               
               
                   
                   
                   
                 CG 
                   
                   
               
               
                   
               
               
                 1497349 
                 45 
                 60 
                 AGATCTA 
                 A ks G es A es T ks   m C es T es A ks   m C es A es A ks G es A es G ks A es T es   m C k   
                 579 
               
               
                   
                   
                   
                 CAAGAG 
                   
                   
               
               
                   
                   
                   
                 ATC 
                   
                   
               
               
                   
               
               
                 1497350 
                 46 
                 61 
                 CAGATCT 
                   m C ks A es G es A ks T es   m C es T ks A es   m C es A ks A es G es A ks G es A es T k   
                 580 
               
               
                   
                   
                   
                 ACAAGA 
                   
                   
               
               
                   
                   
                   
                 GAT 
                   
                   
               
               
                   
               
               
                 1497351 
                 47 
                 62 
                 ACAGATC 
                 A ks C es A e G ks A es T es C ks T es A es C ks A es A es G ks A e G es A k   
                 581 
               
               
                   
                   
                   
                 TACAAGA 
                   
                   
               
               
                   
                   
                   
                 GA 
                   
                   
               
               
                   
               
               
                 1497352 
                 48 
                 63 
                 AACAGAT 
                 A ks A es C es A k G es A es T ks C es T es A ks C es A es A xs G es A e G 
                 582 
               
               
                   
                   
                   
                 CTACAAG 
                   
                   
               
               
                   
                   
                   
                 AG 
                   
                   
               
               
                   
               
               
                 1497353 
                 49 
                 64 
                 GAACAG 
                 G.A es A es C ks A e G e A k T es C es T ks A es C es A ks A e G es A k   
                 583 
               
               
                   
                   
                   
                 ATCTACA 
                   
                   
               
               
                   
                   
                   
                 AGA 
                   
                   
               
               
                   
               
               
                 1497354 
                 50 
                 65 
                 AGAACA 
                 A x G es A es A ks C es A e G ks A es T es C ks T es A es C ks A es A es G k   
                 584 
               
               
                   
                   
                   
                 GATCTAC 
                   
                   
               
               
                   
                   
                   
                 AAG 
                   
                   
               
               
                   
               
               
                 1497355 
                 51 
                 66 
                 GAGAAC 
                 G ks A es G es A ks A es C es A k G es A es T ks C es T es A ks C es A es A k   
                 585 
               
               
                   
                   
                   
                 AGATCTA 
                   
                   
               
               
                   
                   
                   
                 CAA 
                   
                   
               
               
                   
               
               
                 1497356 
                 52 
                 67 
                 AGAGAA 
                 A k G es A es G ks A es A es C ks A es G es A ks T es C es T ks A es C es A x   
                 586 
               
               
                   
                   
                   
                 CAGATCT 
                   
                   
               
               
                   
                   
                   
                 ACA 
                   
                   
               
               
                   
               
               
                 1497357 
                 53 
                 68 
                 TAGAGAA 
                 T ks A es G es A ks G es A es A ksin C es A es G ks A es T es   m C ks T es A es   m C k   
                 587 
               
               
                   
                   
                   
                 CAGATCT 
                   
                   
               
               
                   
                   
                   
                 AC 
                   
                   
               
               
                   
               
               
                 1497359 
                 54 
                 69 
                 TTAGAGA 
                 T ks T es A es G ks A es G es A ks A es C es A ks G es A es T ks C es T es A k   
                 588 
               
               
                   
                   
                   
                 ACAGATC 
                   
                   
               
               
                   
                   
                   
                 TA 
                   
                   
               
               
                   
               
               
                 1497403 
                 54 
                 69 
                 TTAGAGA 
                 T ks T ds A ds G ks A ds G ds A ks A ds C ds A ks G ds A ds T ks C ds T ds A k   
                 588 
               
               
                   
                   
                   
                 ACAGATC 
                   
                   
               
               
                   
                   
                   
                 TA 
               
               
                   
               
            
           
         
       
     
     Example 2: Design of Modified Oligonucleotides Complementary to a SARS-CoV2 Nucleic Acid 
     Modified oligonucleotides were designed as indicated in the tables below. The modified oligonucleotides in the table below 20 nucleosides in length. The sugar motif for the modified oligonucleotides is (from 5′ to 3′): eeeeeeeeeeeeeeeeeeee; wherein each “e” represents a 2′-MOE sugar moiety. The internucleoside linkage motif for the modified oligonucleotides is (from 5′ to 3′): sssssssssssssssssss; wherein each “s” represents a phosphorothioate internucleoside linkage. All cytosine nucleobases throughout each modified oligonucleotide are 5-methylcytosines. 
     “Start site” indicates the 5′-most nucleoside of the target sequence to which the modified oligonucleotide is complementary. “Stop site” indicates the 3′-most nucleoside of the target sequence to which the modified oligonucleotide is complementary. As shown in the tables below, the modified oligonucleotides are 100% complementary to the genomic sequence of severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, designated herein as SEQ ID No:1 (GENBANK Accession No. NC_045512.2). 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Design of uniform MOE modified oligonucleotides 
               
               
                 complementary to severe acute respiratory 
               
               
                 syndrome coronavirus 2 isolate Wuhan-Hu-1 
               
            
           
           
               
               
               
               
               
            
               
                   
                 SEQ 
                 SEQ 
                   
                   
               
               
                   
                 ID NO: 
                 ID NO: 
                   
                 SEQ 
               
               
                 Compound 
                 1 Start 
                 1 Stop 
                 Sequence 
                 ID 
               
               
                 Number 
                 Site 
                 Site 
                 (5&#39; to 3&#39;) 
                 NO 
               
               
                   
               
               
                 1518118 
                 59 
                 78 
                 AAAGTTCGTT 
                 589 
               
               
                   
                   
                   
                 TAGAGAACAG 
                   
               
               
                   
               
               
                 1518119 
                 60 
                 79 
                 TAAAGTTCGT 
                 590 
               
               
                   
                   
                   
                 TTAGAGAACA 
                   
               
               
                   
               
               
                 1518120 
                 61 
                 80 
                 TTAAAGTTCG 
                 591 
               
               
                   
                   
                   
                 TTTAGAGAAC 
                   
               
               
                   
               
               
                 1518121 
                 62 
                 81 
                 TTTAAAGTTC 
                 592 
               
               
                   
                   
                   
                 GTTTAGAGAA 
                   
               
               
                   
               
               
                 329552 
                 63 
                 82 
                 TTTTAAAGTT 
                 593 
               
               
                   
                   
                   
                 CGTTTAGAGA 
                   
               
               
                   
               
               
                 1518123 
                 64 
                 83 
                 ATTTTAAAGT 
                 594 
               
               
                   
                   
                   
                 TCGTTTAGAG 
                   
               
               
                   
               
               
                 1518124 
                 65 
                 84 
                 GATTTTAAAG 
                 595 
               
               
                   
                   
                   
                 TTCGTTTAGA 
                   
               
               
                   
               
               
                 1518125 
                 66 
                 85 
                 AGATTTTAAA 
                 596 
               
               
                   
                   
                   
                 GTTCGTTTAG 
                   
               
               
                   
               
               
                 1518117 
                 58 
                 77 
                 AAGTTCGTTT 
                 597 
               
               
                   
                   
                   
                 AGAGAACAGA 
                   
               
               
                   
               
               
                 330674 
                 56 
                 75 
                 GTTCGTTTAG 
                 598 
               
               
                   
                   
                   
                 AGAACAGATC 
                   
               
               
                   
               
               
                 348271 
                 57 
                 76 
                 AGTTCGTTTA 
                 599 
               
               
                   
                   
                   
                 GAGAACAGAT 
               
               
                   
               
            
           
         
       
     
     Example 3: Activity of Modified Oligonucleotides Complementary to a SARS-CoV-2 RNA, In Vitro, Single Dose 
     Modified oligonucleotides described in the examples above were tested in vitro for activity against SARS-CoV-2. 
     H1437 cells were seeded at a density of 3000 cells/well in 384-well plates and treated with 10 μM of modified oligonucleotide by free uptake for 24 hours. After the 24 hour incubation, the cells were infected with SARS-CoV-2 WA1/2020 strain (BEI resources Catalog #NR-52281) at an MOI of 1 for 48 hours. Two days post infection, the cells were fixed with 4% paraformaldehyde (PFA), permeabilized with 0.03% Triton X-100, and blocked with antibody buffer (1.5% BSA, 1% goat serum, and 0.0025% Tween 20). Following blocking, cells were stained overnight with SARS-CoV-2 nucleoprotein primary antibody (ProSci Catalog #35-579, 1:2000), and then stained with anti-mouse IgG:AlexaFluor 647 secondary (Invitrogen Catalog #A21235, 1:1000), and Hoechst 33342 (Invitrogen Catalog #H3570, 1:2000). The stained cells were imaged to determine infection levels in cells treated with modified oligonucleotides. 
     In separate experiments, H1437 cells were seeded at a density of 3000 cells/well in 384-well plates and treated with 3 μM of modified oligonucleotide by free uptake for 24 hours. After the 24 hour incubation, the modified oligonucleotide was rinsed off the cells, and the cells were infected with SARS-CoV-2 WA1/2020 strain (BEI resources Catalog #NR-52281) at an MOI of 1 for 48 hours. Two days post infection, the cells were fixed with 4% paraformaldehyde (PFA), permeabilized with 0.03% Triton X-100, and blocked with antibody buffer (1.5% BSA, 1% goat serum, and 0.0025% Tween 20). Following blocking, cells were stained overnight with SARS-CoV-2 nucleoprotein primary antibody (ProSci Catalog #35-579, 1:2000) and then stained with anti-mouse IgG:AlexaFluor 647 secondary (Invitrogen Catalog #A21235, 1:1000), and Hoechst 33342 (Invitrogen Catalog #H3570, 1:2000). The stained cells were imaged to determine infection levels in cells treated with modified oligonucleotides. 
     Results are presented in the tables below as percent of the amount of infection of SARS-COV-2 in cells treated with modified oligonucleotide complementary to SARS-COV-2. 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Reduction of SARS-COV-2 infection by modified oligonucleotides 
               
               
                 complementary to SARS-COV-2 in H1437 cells 
               
            
           
           
               
               
               
            
               
                   
                 % infection of SARS-COV-2 
                   
               
            
           
           
               
               
               
            
               
                 Compound No. 
                 no wash (10 μM) 
                 wash (3 μM) 
               
               
                   
               
            
           
           
               
               
               
            
               
                 1497335 
                 0.15 
                 84 
               
               
                 1497418 
                 0.12 
                 93 
               
               
                 1497427 
                 0.13 
                 94 
               
               
                 1497438 
                 0.85 
                 89 
               
               
                 1497449 
                 2.15 
                 87 
               
               
                 1497460 
                 3.69 
                 103 
               
               
                 1497470 
                 1.12 
                 102 
               
               
                 1497480 
                 0.14 
                 90 
               
               
                 1497336 
                 0.15 
                 98 
               
               
                 1497347 
                 0.23 
                 97 
               
               
                 1497358 
                 0.10 
                 106 
               
               
                 1497366 
                 0.25 
                 93 
               
               
                 1497377 
                 0.14 
                 84 
               
               
                 1497388 
                 0.13 
                 93 
               
               
                 1497399 
                 2.15 
                 102 
               
               
                 1497404 
                 0.29 
                 100 
               
               
                 1497405 
                 0.14 
                 96 
               
               
                 1497406 
                 0.21 
                 95 
               
               
                 1497408 
                 1.34 
                 95 
               
               
                 1497409 
                 0.54 
                 94 
               
               
                 1497410 
                 1.21 
                 88 
               
               
                 1497411 
                 10.88 
                 100 
               
               
                 1497412 
                 32.53 
                 95 
               
               
                 1497413 
                 6.08 
                 102 
               
               
                 1497414 
                 23.41 
                 96 
               
               
                 1497415 
                 10.88 
                 98 
               
               
                 1497416 
                 15.76 
                 99 
               
               
                 348264 
                 16.46 
                 90 
               
               
                 1497419 
                 29.92 
                 86 
               
               
                 348265 
                 13.58 
                 97 
               
               
                 1497421 
                 2.64 
                 95 
               
               
                 348266 
                 4.36 
                 87 
               
               
                 1497423 
                 7.78 
                 84 
               
               
                 348267 
                 21.20 
                 92 
               
               
                 1497425 
                 29.24 
                 97 
               
               
                 348268 
                 54.82 
                 97 
               
               
                 1497491 
                 33.35 
                 81 
               
               
                 330674 
                 6.05 
                 88 
               
               
                 348271 
                 2.34 
                 92 
               
               
                 1518117 
                 0.66 
                 98 
               
               
                 1518118 
                 2.34 
                 80 
               
               
                 1518119 
                 7.90 
                 86 
               
               
                 1518120 
                 3.24 
                 93 
               
               
                 1518121 
                 1.93 
                 91 
               
               
                 329552 
                 4.24 
                 87 
               
               
                 1518123 
                 1.57 
                 82 
               
               
                 1518124 
                 0.30 
                 94 
               
               
                 1518125 
                 0.54 
                 94 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Reduction of SARS-COV-2 infection by modified oligonucleotides 
               
               
                 complementary to SARS-COV-2 in H1437 cells 
               
            
           
           
               
               
               
            
               
                   
                 % infection of SARS-COV-2 
                   
               
            
           
           
               
               
               
            
               
                 Compound No. 
                 no wash (10 μM) 
                 wash (3 μM) 
               
               
                   
               
            
           
           
               
               
               
            
               
                 1495585 
                 0.10 
                 79 
               
               
                 1495586 
                 0.16 
                 91 
               
               
                 1495597 
                 2.75 
                 91 
               
               
                 1495699 
                 2.28 
                 85 
               
               
                 1495700 
                 45.97 
                 81 
               
               
                 1495701 
                 0.26 
                 97 
               
               
                 1495702 
                 1.82 
                 99 
               
               
                 1495704 
                 13.15 
                 86 
               
               
                 1495471 
                 31.66 
                 94 
               
               
                 1495473 
                 86.39 
                 94 
               
               
                 1495474 
                 2.59 
                 103 
               
               
                 1495476 
                 31.93 
                 90 
               
               
                 1495478 
                 0.02 
                 82 
               
               
                 1495479 
                 0.00 
                 90 
               
               
                 1495480 
                 9.70 
                 100 
               
               
                 1495482 
                 6.97 
                 99 
               
               
                 1495483 
                 68.76 
                 95 
               
               
                 1495484 
                 0.58 
                 91 
               
               
                 1495485 
                 0.89 
                 93 
               
               
                 1495487 
                 1.07 
                 94 
               
               
                 1495489 
                 12.80 
                 86 
               
               
                 1495490 
                 10.34 
                 98 
               
               
                 1495491 
                 65.10 
                 93 
               
               
                 1495493 
                 0.04 
                 100 
               
               
                 1495494 
                 0.21 
                 95 
               
               
                 1495495 
                 1.08 
                 97 
               
               
                 1495496 
                 4.87 
                 95 
               
               
                 1495497 
                 0.02 
                 86 
               
               
                 1495499 
                 34.95 
                 83 
               
               
                 1495500 
                 64.29 
                 95 
               
               
                 1495501 
                 42.24 
                 93 
               
               
                 1495503 
                 0.07 
                 85 
               
               
                 1495505 
                 0.08 
                 83 
               
               
                 1495507 
                 0.82 
                 90 
               
               
                 1495509 
                 2.48 
                 94 
               
               
                 1495510 
                 0.73 
                 96 
               
               
                 1495511 
                 0.02 
                 79 
               
               
                 1495512 
                 3.65 
                 86 
               
               
                 1495513 
                 0.04 
                 89 
               
               
                 1495516 
                 0.01 
                 95 
               
               
                 1495517 
                 0.27 
                 78 
               
               
                 1495518 
                 4.07 
                 85 
               
               
                 1495519 
                 3.63 
                 89 
               
               
                 1495524 
                 14.21 
                 86 
               
               
                 1495525 
                 1.35 
                 84 
               
               
                 1495526 
                 2.79 
                 79 
               
               
                 1495529 
                 0.03 
                 92 
               
               
                 1495531 
                 0.03 
                 91 
               
               
                 1495532 
                 0.19 
                 79 
               
               
                 1495536 
                 31.54 
                 92 
               
               
                 1495537 
                 0.05 
                 84 
               
               
                 1495539 
                 3.31 
                 89 
               
               
                 1495540 
                 0.10 
                 79 
               
               
                 1495541 
                 4.59 
                 83 
               
               
                 1495542 
                 1.54 
                 80 
               
               
                 1495546 
                 19.63 
                 84 
               
               
                 1495549 
                 0.42 
                 87 
               
               
                 1495552 
                 0.71 
                 88 
               
               
                 1495553 
                 1.62 
                 83 
               
               
                 1495564 
                 1.62 
                 85 
               
               
                 1495567 
                 0.22 
                 84 
               
               
                 1495568 
                 0.15 
                 97 
               
               
                 1495569 
                 0.17 
                 85 
               
               
                 1495572 
                 0.06 
                 92 
               
               
                 1495574 
                 0.23 
                 103 
               
               
                 1495576 
                 0.05 
                 105 
               
               
                 1495577 
                 0.07 
                 74 
               
               
                 1495579 
                 1.27 
                 79 
               
               
                 1495581 
                 53.89 
                 104 
               
               
                 1495583 
                 18.24 
                 95 
               
               
                 1495584 
                 59.01 
                 90 
               
               
                 1495588 
                 11.22 
                 90 
               
               
                 1495589 
                 1.30 
                 91 
               
               
                 1495590 
                 0.24 
                 98 
               
               
                 1495591 
                 5.89 
                 85 
               
               
                 1495592 
                 0.46 
                 91 
               
               
                 1495593 
                 4.70 
                 107 
               
               
                 1495594 
                 13.05 
                 107 
               
               
                 1495596 
                 2.09 
                 84 
               
               
                 1495600 
                 0.13 
                 82 
               
               
                 1495603 
                 0.35 
                 102 
               
               
                 1495604 
                 0.28 
                 101 
               
               
                 1495605 
                 0.09 
                 75 
               
               
                 1495606 
                 3.97 
                 99 
               
               
                 1495607 
                 0.18 
                 98 
               
               
                 1495608 
                 3.15 
                 103 
               
               
                 1495609 
                 0.97 
                 88 
               
               
                 1495610 
                 1.05 
                 89 
               
               
                 1495611 
                 0.71 
                 94 
               
               
                 1495612 
                 27.10 
                 108 
               
               
                 1495616 
                 5.06 
                 78 
               
               
                 1495617 
                 0.73 
                 86 
               
               
                 1495619 
                 0.50 
                 101 
               
               
                 1495620 
                 0.40 
                 102 
               
               
                 1495621 
                 0.40 
                 82 
               
               
                 1495622 
                 0.69 
                 89 
               
               
                 1495623 
                 0.24 
                 95 
               
               
                 1495624 
                 0.55 
                 106 
               
               
                 1495625 
                 0.43 
                 76 
               
               
                 1495627 
                 48.46 
                 87 
               
               
                 1495628 
                 8.88 
                 93 
               
               
                 1495629 
                 80.27 
                 100 
               
               
                 1495630 
                 29.49 
                 73 
               
               
                 1495631 
                 51.80 
                 80 
               
               
                 1495632 
                 3.39 
                 87 
               
               
                 1495634 
                 6.39 
                 92 
               
               
                 1495640 
                 0.29 
                 72 
               
               
                 1495641 
                 0.23 
                 78 
               
               
                 1495642 
                 0.45 
                 90 
               
               
                 1495644 
                 0.52 
                 96 
               
               
                 1495647 
                 0.43 
                 70 
               
               
                 1495648 
                 0.18 
                 87 
               
               
                 1495649 
                 0.24 
                 93 
               
               
                 1495651 
                 16.56 
                 99 
               
               
                 1495652 
                 6.82 
                 73 
               
               
                 1495653 
                 44.06 
                 80 
               
               
                 1495656 
                 2.25 
                 83 
               
               
                 1495658 
                 0.23 
                 91 
               
               
                 1495659 
                 0.88 
                 119 
               
               
                 1495661 
                 0.13 
                 120 
               
               
                 1495662 
                 0.48 
                 125 
               
               
                 1495664 
                 54.89 
                 127 
               
               
                 1495667 
                 0.21 
                 125 
               
               
                 1495669 
                 17.29 
                 112 
               
               
                 1495671 
                 1.07 
                 81 
               
               
                 1495672 
                 6.40 
                 96 
               
               
                 1495673 
                 14.27 
                 88 
               
               
                 1495675 
                 5.92 
                 91 
               
               
                 1495676 
                 14.37 
                 82 
               
               
                 1495678 
                 56.56 
                 85 
               
               
                 1495681 
                 20.73 
                 82 
               
               
                 1495689 
                 0.07 
                 89 
               
               
                   
               
            
           
         
       
     
     Example 4: Activity of Modified Oligonucleotides Complementary to a SARS-CoV-2 RNA, In Vitro, Single Dose 
     Modified oligonucleotides described in the examples above were tested in vitro for activity against SARS-CoV-2. 
     Compound No. 792169, a control modified oligonucleotide with a sequence (from 5′ to 3′) of CGCCGATAAGGTACAC (SEQ ID NO: 600), was designed to not target SARS-CoV-2. The sugar motif for Compound No. 792169 is (from 5′ to 3′): kkkddddddddddkkk; wherein each “d” represents a 2′-β-D-deoxyribosyl sugar moiety, and each “k” represents a cEt modified sugar moiety. The internucleoside linkage motif for Compound No. 792169 is (from 5′ to 3′): sssssssssssssss; wherein each “s” represents a phosphorothioate internucleoside linkage. Each cytosine residue is a 5-methylcytosine. 
     H1437 cells were seeded at a density of 3000 cells/well in 384-well plates and treated with 10 μM of modified oligonucleotide by free uptake for 24 hours. After the 24 hour incubation, the modified oligonucleotide was rinsed off the cells, and the cells were infected with SARS-CoV-2 WA1/2020 strain (BEI resources Catalog #NR-52281) at an MOI of 1 for 48 hours. Two days post infection, the cells were fixed with 4% paraformaldehyde (PFA), permeabilized with 0.03% Triton X-100, and blocked with antibody buffer (1.5% BSA, 1% goat serum, and 0.0025% Tween 20). Following blocking, cells were stained overnight with SARS-CoV-2 nucleoprotein primary antibody (ProSci Catalog #35-579, 1:2000) and then stained with anti-mouse IgG:AlexaFluor 647 secondary (Invitrogen Catalog #A21235, 1:1000), and Hoechst 33342 (Invitrogen Catalog #H3570, 1:2000). The stained cells were imaged to determine infection levels in cells treated with modified oligonucleotides. Compound No. 792169 was added to the experiment as a negative control. 
     Results are presented in the tables below as percent of the amount of infection of SARS-COV-2 in cells treated with modified oligonucleotide that targets SARS-COV-2. 
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 Reduction of SARS-COV-2 infection by modified oligonucleotides 
               
               
                 complementary to SARS-COV-2 in H1437 cells 
               
            
           
           
               
               
               
            
               
                   
                 Compound Number 
                 SARS-COV-2 % infection 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 1495577 
                 2 
               
               
                   
                 1495511 
                 7 
               
               
                   
                 1495478 
                 9 
               
               
                   
                 1495647 
                 18 
               
               
                   
                 1495600 
                 19 
               
               
                   
                 1495671 
                 20 
               
               
                   
                 1495676 
                 26 
               
               
                   
                 1495616 
                 28 
               
               
                   
                 1495517 
                 29 
               
               
                   
                 1495532 
                 29 
               
               
                   
                 1495681 
                 31 
               
               
                   
                 1495540 
                 32 
               
               
                   
                 1495605 
                 34 
               
               
                   
                 1495625 
                 34 
               
               
                   
                 1495579 
                 37 
               
               
                   
                 1495585 
                 37 
               
               
                   
                 1495640 
                 38 
               
               
                   
                 1495621 
                 43 
               
               
                   
                 1495652 
                 44 
               
               
                   
                 1495641 
                 46 
               
               
                   
                 1495526 
                 52 
               
               
                   
                 1495630 
                 53 
               
               
                   
                 1495653 
                 57 
               
               
                   
                 1495700 
                 65 
               
               
                   
                 1495631 
                 71 
               
               
                   
                 1495542 
                 71 
               
               
                   
                 792169 
                 40 
               
               
                   
                   
               
            
           
         
       
     
     Example 5: Activity of Modified Oligonucleotides Complementary to a SARS-CoV-2 RNA, In Vitro, Multiple Dose 
     Modified oligonucleotides described in the examples above were tested in vitro for activity against SARS-CoV-2. 
     H1437 cells were seeded at a density of 3000 cells/well in 384-well plates and treated with modified oligonucleotide by free uptake for 24 hours at doses indicated in the table below. After the 24 hour incubation, the modified oligonucleotide was rinsed off the cells, and the cells were infected with SARS-CoV-2 WA1/2020 strain (BEI resources Catalog #NR-52281) at an MOI of 1 for 48 hours. Two days post infection, the cells were fixed with 4% paraformaldehyde (PFA), permeabilized with 0.03% Triton X-100, and blocked with antibody buffer (1.5% BSA, 1% goat serum, and 0.0025% Tween 20). Following blocking, cells were stained overnight with SARS-CoV-2 nucleoprotein primary antibody (ProSci Catalog #35-579, 1:2000) and then stained with anti-mouse IgG:AlexaFluor 647 secondary (Invitrogen Catalog #A21235, 1:1000), and Hoechst 33342 (Invitrogen Catalog #H3570, 1:2000). The stained cells were imaged to determine infection levels in cells treated with modified oligonucleotides. Compound No. 792169 (described herein above) was added to the experiment as a negative control. 
     Results are presented in the tables below as percent of the amount of infection of SARS-COV-2 in cells treated with modified oligonucleotide complementary to SARS-COV-2. 
     
       
         
           
               
             
               
                 TABLE 9 
               
             
            
               
                   
               
               
                 Reduction of SARS-COV-2 infection by modified oligonucleotides 
               
               
                 complementary to SARS-COV-2 in H1437 cells 
               
            
           
           
               
               
               
            
               
                 Compound Number 
                 Dose (ug) 
                 SARS-COV-2 % infection 
               
               
                   
               
            
           
           
               
               
               
            
               
                 1495478 
                 10 
                 13 
               
               
                   
                 3 
                 35 
               
               
                   
                 1 
                 48 
               
               
                   
                 0.3 
                 39 
               
               
                 1495511 
                 10 
                 13 
               
               
                   
                 3 
                 68 
               
               
                   
                 1 
                 76 
               
               
                   
                 0.3 
                 72 
               
               
                 1495577 
                 10 
                 7 
               
               
                   
                 3 
                 57 
               
               
                   
                 1 
                 74 
               
               
                   
                 0.3 
                 95 
               
               
                 1497335 
                 10 
                 25 
               
               
                   
                 3 
                 60 
               
               
                   
                 1 
                 78 
               
               
                   
                 0.3 
                 104 
               
               
                 1497377 
                 10 
                 34 
               
               
                   
                 3 
                 70 
               
               
                   
                 1 
                 91 
               
               
                   
                 0.3 
                 113 
               
               
                 792169 
                 10 
                 59 
               
               
                   
                 3 
                 79 
               
               
                   
                 1 
                 96 
               
               
                   
                 0.3 
                 110