SII-SWORD/CoKE huggingface dataset:
Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like (Spike_S1_N_SARS-CoV-like)
Type: Domain

This entry represents the N-terminal domain (NTD) of the S1 subunit of the Spike (S) proteins from betacoronaviruses in the sarbecovirus subgenera (B lineage), including the highly pathogenic human coronavirus (CoV), Severe acute respiratory syndrome (SARS) CoV, and SARS-CoV-2, also known as a 2019 novel coronavirus (2019-nCoV) or COVID-19 virus .

The CoV Spike (S) protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesised as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). Most CoVs, including SARS-CoV-2, SARS-CoV, and MERS-CoV use the C-domain to bind their receptors. However, CoV such as mouse hepatitis virus (MHV) uses the NTD to bind its receptor, mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a). The S1 NTD contributes to the Spike trimer interface .
Orf10 protein, SARS-CoV-2 (Orf10_SARS-CoV-2)
Type: Family

This entry represents the Orf10 protein of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). SARS-CoV-2 causes the disease called "coronavirus disease 2019" (COVID-19). Orf10 appears to have no homologous proteins in SARS-CoV and other coronaviruses and is uniquely expressed in SARS-CoV-2 . Recently, it was reported that Orf10 suppresses the IFN-I signalling pathway through the interaction with mitochondrial antiviral signalling protein (MAVS), which is degraded via Orf10-induced autophagy pathway. Orf10 interacts with NIX and LC3B and induces mitophagy .
Nonstructural protein 13, 1B domain, coronavirus (NSP13_1B_dom_CoV)
Type: Domain

Helicase nonstructural protein 13 (NSP13) is encoded by the replicase polyprotein 1a/ab of coronaviruses and released after a proteolytic process. It plays a vital role in catalysing the unwinding of duplex oligonucleotides into single strands in an NTP-dependent manner. It is a multidomain protein which includes an N-terminal Cys/His rich zinc-binding domain (ZBD), followed by a stalk and 1B domains, and a helicase core that belongs to the superfamily SF1 of helicases, containing two RecA1 and RecA2 domains . The stalk region connects the ZBD domain and 1B domain. Nsp13 adopts a triangular pyramid shape in which the two RecA1 and A2 and 1B domain form the triangular base, while N-terminal ZBD and stalk domains are arranged at the apex of the pyramid . Recently, it has been reported that SARS-CoV-2 NSP13 as an interferon antagonist. It is involved in type I interferon (IFN-I) response as it binds and blocks TBK1 phosphorylation to inhibit interferon regulatory factor 3 (IRF3) which results in decreased IRF3 activation .

This entry represents the 1B domain, which has a regulatory role modulating the nucleic acid substrate binding. Based on the structures from the related Equine arteritis virus (EAV) NSP10, it is likely that 1B domain forms a channel together with 1A and 2A domains that accommodates the single stranded nucleic acids .
Nucleocapsid (N) protein, C-terminal domain, coronavirus (N_prot_C_CoV)
Type: Domain

The Nucleocapsid (N) protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signalling pathways. The N protein interacts with genomic and subgenomic RNA molecules. Together with the envelope protein M, it participates in genome condensation and packaging. The N protein is a highly immunogenic and abundantly expressed protein during infection, capable of inducing protective immune responses against SARS-CoV and SARS-CoV-2 .

Coronavirus (CoV) nucleocapsid (N) proteins have 3 highly conserved domains. The N-terminal domain (NTD) (N1b), the C-terminal domain (CTD)(N2b) and the N3 region. The N1b and N2b domains from SARS CoV, infectious bronchitis virus (IBV), human CoV 229E and mouse hepatic virus (MHV) display similar topological organisations. N proteins form dimers, which are asymmetrically arranged into octamers via their N2b domains . Both domains contribute to the binding of viral RNA genome .

This entry represents the C-terminal domain of the nucleocapsid proteins from Coronavirus. The C-terminal domain of the N protein (N-CTD) is involved in dimerization, and is thus, also called the dimerization domain . Structurally, the C-terminal domain forms a tightly intertwined dimer with an intermolecular four-stranded central β-sheet platform flanked by α helices, indicating that the basic building block for coronavirus nucleocapsid formation is a dimeric assembly of N protein .
Nucleocapsid (N) protein, N-terminal domain, coronavirus (N_prot_N_CoV)
Type: Domain

The Nucleocapsid (N) protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signalling pathways. The N protein interacts with genomic and subgenomic RNA molecules. Together with the envelope protein M, it participates in genome condensation and packaging. The N protein is a highly immunogenic and abundantly expressed protein during infection, capable of inducing protective immune responses against SARS-CoV and SARS-CoV-2 .

Coronavirus (CoV) nucleocapsid (N) proteins have 3 highly conserved domains. The N-terminal domain (NTD) (N1b), the C-terminal domain (CTD)(N2b) and the N3 region. The N1b and N2b domains from SARS CoV, infectious bronchitis virus (IBV), human CoV 229E and mouse hepatic virus (MHV) display similar topological organisations. N proteins form dimers, which are asymmetrically arranged into octamers via their N2b domains . Both domains contribute to the binding of viral RNA genome .

This entry represents the N-terminal domain of the nucleocapsid (N) protein predominantly from Coronavirus. It exhibits a U-shaped structure, with two arms rich in basic residues, providing a module for specific interaction with RNA . The overall structure of the N-terminal domain found in SARS-CoV-2 is similar to other reported coronavirus nucleocapsid protein N-terminal domains, but the surface charge distribution patterns are different. This domain also interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. It has been identified as an important drug target .
M matrix/glycoprotein, deltacoronavirus (M_deltaCoV)
Type: Family

M proteins play a critical role in protein-protein interactions (as well as protein-RNA interactions) since virus-like particle (VLP) formation in many coronavirus requires only the M and envelope (E) proteins for efficient virion assembly . The M protein or E1 glycoprotein is implicated in virus assembly . The E1 viral membrane protein is required for formation of the viral envelope and is transported via the Golgi complex .

This entry contains the Membrane (M) protein of deltacoronaviruses, including porcine deltacoronavirus and Bulbul coronavirus HKU11 .
RNA-dependent RNA polymerase, coronavirus HKU1-like (RdRp_HCoV_HKU1-like)
Type: Domain

This entry contains the RNA-dependent RNA polymerase (RdRp) of human coronavirus HKU1, murine hepatitis virus, and similar proteins from betacoronaviruses in the embecovirus subgenera (A lineage).

Coronaviruses (CoVs) utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (NSPs) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as NSP12), catalyses the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, NSP7 and NSP8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. NSP12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RpRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides .
Nonstructural protein 10, 1B domain, arterivirus (NSP10_1B_Av)
Type: Domain

Nidoviruses (Coronaviridae, Arteriviridae, and Roniviridae) feature the most complex genetic organization among plus-strand RNA viruses. Their replicase genes encode an exceptionally large replicase polyprotein 1a/ab which is then proteolytically processed to release different nonstructural proteins (NSPs) that mediate the key functions required for replication and transcription. One of these NSPs, called NSP10 in arteriviruses (Av) and NSP13 in coronaviruses (CoV) functions as a helicase . It is a multidomain protein consisting of a N-terminal Cys/His rich zinc-binding domain (ZBD) and a helicase core that belongs to the superfamily SF1 of helicases. The helicase core contains two RecA1 and RecA2 domains and a 1B domain .

This entry represents the 1B domain, which has a regulatory role modulating the nucleic acid substrate binding. Based on the structures from the Equine arteritis virus (EAV) NSP10, 1B domain undergoes large conformational change upon substrate binding, and forms a channel together with 1A and 2A domains that accommodates the single stranded nucleic acids .
RNA-dependent RNA polymerase, bat coronavirus HKU9-like (RdRp_batCoV_HKU9-like)
Type: Domain

This entry contains the RNA-dependent RNA polymerase (RdRp) of bat coronavirus HKU9 and similar proteins from betacoronaviruses in the nobecovirus subgenera (D lineage).

Coronaviruses (CoVs) utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (NSPs) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as NSP12), catalyses the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, NSP7 and NSP8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. NSP12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RpRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides .
RNA-dependent RNA polymerase, Middle East respiratory syndrome-related coronavirus (RdRp_MERS-CoV-like)
Type: Domain

This entry contains the RNA-dependent RNA polymerase (RdRp) of Middle East respiratory syndrome (MERS)-related CoV, bat-CoV HKU5, and similar proteins from betacoronaviruses in the merbecovirus subgenera (C lineage).

Coronaviruses (CoVs) utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (NSPs) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as NSP12), catalyses the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, NSP7 and NSP8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. NSP12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RpRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides .
RNA-dependent RNA polymerase, SARS-CoV-like (RdRp_SARS-CoV-like)
Type: Domain

This entry contains the RNA-dependent RNA polymerase (RdRp) of Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus), and similar proteins from betacoronaviruses in the sarbecovirus subgenera (B lineage).

Coronaviruses (CoVs) utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (NSPs) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as NSP12), catalyses the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, NSP7 and NSP8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. NSP12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RpRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides .
Non-structural protein NSP3, SUD-C domain, bat CoV HKU9-like (Nsp3_SUD_C_HKU9_CoV)
Type: Domain

This entry represents the SUD-C domain of Rousettus bat coronavirus (CoV) HKU9 non-structural protein 3 (NSP3) and other NSP3s from betacoronaviruses in the nobecovirus subgenera (D lineage).

NSP3 of SARS coronavirus includes a SARS-unique domain (SUD) consisting of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. SUD-N and SUD-M are macro domains which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides) . SUD is not as specific to SARS CoV as originally thought and is also found in Rousettus bat CoV HKU9 and related bat CoVs . Similar to SARS SUD-C, Rousettus bat CoV HKU9 SUD-C (HKU9 C), also adopts a frataxin-like fold that has structural similarity to DNA-binding domains of DNA-modifying enzymes. However, there is little sequence similarity between the two domains. SARS SUD-C has been shown to bind to single-stranded RNA and recognize purine bases more strongly than pyrimidine bases; it also regulates the RNA binding behavior of the SARS SUD-M macrodomain. It is not known whether HKU9 C functions in the same way .
NSP3, second ubiquitin-like (Ubl) domain, coronavirus (Nsp3_Ubl2_dom_CoV)
Type: Domain

Non-structural protein NSP3 is a multi-domain protein, the largest product of coronavirus ORF1a which encodes the poyprotein 1a/1ab (pp1a/1ab). NSP3 is released from pp1a/1ab by the papain-like protease domain(s), which is (are) part of NSP3 itself. NSP3 plays many roles in the viral life cycle. It can act as a scaffold protein to interact with itself and to bind other viral Nsps or host proteins. In particular, Nsp3 is essential for the formation of the the replication/ transcription complex (RTC). The RTC associates with host ER membranes producing convoluted membranes and double-membrane vesicles. It is also involved in post-translational modifications of host proteins to antagonise its innate immune response .

NSP3 comprises up to 16 different domains and regions, their organisation differs between coronaviruses (CoV). However, eight domains and two transmembrane regions are conserved in all known CoVs: the ubiquitin-like domain 1 (Ubl1), the Glu-rich acidic domain (hypervariable region), a macrodomain (X domain), the ubiquitin-like domain 2 (Ubl2), the papain-like protease 2 (PL2pro, depending on the CoV there are one or two PLpro), the NSP3 ectodomain (3Ecto, also called "zinc-finger domain"), as well as the domains Y1, Y2 and Y3 of unknown functions. The Y1 domain is conserved in all viruses of the order Nidovirales, while Y2 and Y3 are conserved in all coronaviruses. The three domains from the Y region (Y1 to Y3) are located at the cytosolic side of the ER. The level of their conservation is close to that for the enzymatic domains of Nsp3 and exceeds nonenzymatic ones. From the consistently high conservation of Y1, Y2, and Y3, it has been hypothesize that Y1 to Y3 may form a single functional unit with a conserved enzymatic function .

Nsp3 comprises various domains of functional and structural importance for virus replication, the organization of which differs between CoV genera, due to duplication or absence of some domains . Two ubiquitin-like domains, Ubl1 and Ubl2 (Nsp3a and the N-terminal domain of Nsp3d), exist within Nsp3 of all CoVs. The known functional roles of Nsp3a Ubl in CoVs are related to single-stranded (ssRNA) binding and interacting with the nucleocapsid (N) protein . Nsp3d Ubl is immediately adjacent to the N terminus of the PLpro (or PL2Pro) domain in CoV polyproteins, and it may play a critical role in protease regulation and stability as well as in viral infection . In addition to the four β-strands and two α-helices that are common to ubiquitin-like folds, the Nsp3a Ubl domain contains two short helices . The Nsp3d Ubl domain comprises five β-strands, one α-helix, and one 3(10)-helix . This entry represents a domain covering the entire CoV Nsp3a and Nsp3d second Ubl domain. Its exact function is unclear, but it might act as a modulator helping the PL2pro recognise its specific targets during coronavirus infection .
RNA-dependent RNA polymerase, deltacoronavirus (RdRp_deltaCoV)
Type: Domain

This entry contains the RNA-dependent RNA polymerase (RdRp) of deltacoronaviruses.

Coronaviruses (CoVs) utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (NSPs) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as NSP12), catalyses the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, NSP7 and NSP8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. NSP12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RpRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides .
SF1 helicase, uncharacterised linker domain, tornidovirus (SF1_Hel_unc_tv)
Type: Domain

This entry represents an uncharacterised domain found in SF1 helicases from tornidovirus, including Breda virus serotype 1. This group of viruses belong to Nidovirales order and it shares the same genome organisation. It encodes the large polyprotein pp1a which is then proteolytically processed to produce the enzymes required for the replicative machinery. This is a novel cluster of nidoviruses that significantly diverged from toroviruses and, even more, from coronaviruses, roniviruses, and arteriviruses . This domain connects the zinc-binding domain (ZBD) with the first helicase domain, resembling that of the 1B domain in SARS-Nsp13 helicase .
RNA-dependent RNA polymerase, alphacoronavirus (RdRp_alphaCoV)
Type: Domain

This entry contains the RNA-dependent RNA polymerase (RdRp) of alphacoronaviruses, including human coronaviruses (HCoVs), HCoV-NL63, and HCoV-229E.

CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as NSP12), catalyses the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, NSP7 and NSP8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir .

NSP12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RpRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides .
RNA-dependent RNA polymerase, gammacoronavirus (RdRp_gammaCoV)
Type: Domain

This entry contains the RNA-dependent RNA polymerase (RdRp) of gammacoronaviruses, including the RdRp of avian infectious bronchitis virus (IBV) and similar proteins.

CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as NSP12), catalyses the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, NSP7 and NSP8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir .

NSP12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RpRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides .