Viral Challenges, Innovative Solutions: Novel Strategies in the Control of  Emerging and Established Diseases
Creators: name: Atta Muhammad, Sumaira
name: Khaliq, Hafiz Muhammad Haseeb
name: Rana, Sidra
name: Ashraf, Maria
Publisher: name: Zenodo
Year: 2023

description: ABSTRACT: The management and control of viral diseases is crucial for global health. We discussed different strategies for controlling emerging and existing viral diseases in this article, such as antiviral drugs, vaccination, gene editing and nanotechnology. For example, antiviral drugs have been developed to treat viral infections such as hepatitis C, HIV, and influenza. Vaccines have been effective in controlling viral infections such as measles, Hepatitis B and polio. Specific viruses can be targeted by engineered nanoparticles which can inhibit their replication, possibly providing a new approach to antiviral therapy. Gene editing technologies, for example, CRISPR-Cas9 can be used to target viral genomes and disable the virus. Moreover, we discuss the use of monoclonal antibodies, convalescent plasma, and plant-based production systems as emerging strategies for controlling viral diseases. Overall, the development of new and innovative strategies is crucial for the effective control and management of both existing and emerging viral diseases.
description: INTRODUCTION: Infectious diseases are major cause of mortality and morbidity in human and animals (Mourya et al., 2019). Every country has experienced the outbreaks and epidemics of many viral infectious diseases. Viruses are molecular parasite or symbionts consists of nucleic acid molecule in protein coat that evolve with nearly all form of cellular life (Koonin et al., 2020). There are millions of different types of viruses on Earth but <7000 types have been described in detail. NCBI virus genome database has >193,000 complete genome sequence, but still doubtlessly many more to discover. There are billions of different types of viruses. Viral genome type determined viral replication route and protein expression.Rotavirus, CMV (Cytomegalovirus), Measles are existing viral diseases, while Corona virus (including COVID-19), SFTS virus, Zika virus, and West Nile virus are emerging viral diseases. Vaccines are available for some Viruses such as Rotarix® vaccine contain single human rotavirus strain(P1A[8], G1) for Rotavirus (Rotavirus vaccines WHO position paper: January 2013 - Recommendations‘, 2013).RNA viruses known for worst pandemics for mankind, including outbreaks of Ebola and COVID-19, Major Challenge to design RNA viruses vaccines is the fact they are extremely genetically diverse (Kustin and Stern, 2021. However, the vaccine has still managed to make a considerable impact, with a 75% reduction in deaths among children from 2000 to 2012 (Simons et al., 2012). SFTS virus (Severe Fever with thrombocytopenia syndrome virus) is an emerging tick-borne virus, West Nile virus and Zika virus are emerging mosquito-borne viruses.

ROTAVIRUS : Rotavirus belong to Reoviridae family, which is family of  11 segmented ds RNA viruses (Carvalho-Costa et al., 2019). The Reoviridae is divided into two subfamilies, Rotaviruses are partof Sedoreovirinae sub family. Rotaviruses are triple-layeredouter capsid layer composed of two structural proteins VP7 and VP4, middle layer composed of two non-structural protein VP6 and VP2 and innermost layer composed of the viral genome and several proteins including VP1, VP2 and VP3 (Binka et al., 2003). There are three serologic types on basis of different antigenic determinants on the outer capsid protein (Medical Microbiology and Immunology). Due to their genetic and antigenic properties Rotavirus has been classified in seven heterogenic groups (Alam et al., 2013).

EPIDEMIOLOGY AND TRANSMISSION: Rotavirus caused worldwide infections (WHO 2018). Pakistan harbors high level disease burden of gastro-enteric infections, majority of these infections caused by Rota virus (Alam et al., 2013). 95% of Rota virus associated deaths were reported in Africa and Asian countries (Alam et al., 2013). In 2008, Rotavirus gastroenteritis caused 4,53,000 deaths of children worldwide (WHO). Globally 114 million Rotavirus cases were reported in children <5 years of age in 2003(Crawford et al., 2017). 41% Rotavirus hospitalized cases were reported in infants at 8 months of age in Africa and 40% globally (Madhi et al., 2016). Rotavirus infections usually starts within two days after virus entry into body and cause fever, nausea, vomiting, watery diarrhoea, abdominal pain and gastroenteritis (WHO 2017). Rotavirus diarrhoea and dehydration are main symptoms among young children (M. Irfan Habib el at., 2014). In healthy adults, rotavirus causes only mild symptoms (WHO 2018). Main transmission of Rotavirus is mainly by the fecal-oral route but directly from person to person, indirectly via contaminated fomites also occur (Dennehy, 2000).

DIAGNOSIS: 1. Enzyme Linked Immunosorbent Assay (ELISA) detect the inner capsid antigen (VP6) in stool and many commercial ELISA kits are available (Page, Nadan and Mans, 2019). 2. RT-PCR (Real Time-Polymerase Chain Reaction)  3. Polyacrylamide gel electrophoresis. 4. Electron Microscopy. Routine diagnosis of Rotavirus done by detection of rotavirus in stool sample by using ELISA method (Miño et al., 2015). RT-PCR based detect RNA of rotavirus in stool is more sensitive method (Crawford et al., 2017).

TREATMENT AND PREVENTION: There is no specific medication to treat rotavirus infections. Oral rehydration therapy is given to patients with severe diarrhoea (Hassine-Zaafrane and Aouni, 2012). Rotavirus infections occur in all children in developing countries at early age, good hygiene and proper sanitation alone are considered insufficient for prevention (Patel et al., 2012). Local government developed and licensed six Rotavirus vaccines, only two vaccines recommended by WHO (Wang et al., 2021). Rotarix® contain single human rotavirus strain (P1A[8], G1), two oral doses of Rotarix® two doses is given to children at 2 months and 4 months of ages (Rotavirus vaccines WHO position paper: January 2013 - Recommendations‘, 2013). RotaTeq® contains five rotavirus strains. Three oral doses of RotaTeq® is given to children at age of 6-12weeks first dose is given, 4-10 weeks second dose is given and 32 weeks third dose is given (Parashar, Nelson and Kang, 2013).

MEASLES: Measles, also known as rubeola (Latin: Rubeo= Red), is very infections, contagious and acute feverish diseases caused by single-stranded RNA enveloped virus (A. K. C. Leung et al., 2018). The virus belongs to the Morbillivirus genus in the paramyxoviridae family (Abad & Safdar, 2015). It is estimated that the cases of Measles occur almost 20 million annually, hence it is widespread in world‘s population (Clemmons et al., 2015). For more than 40 years, a safe and efficient vaccine was available but still measles was a major cause of fatalities in young children worldwide. However, the vaccine has still managed to make a considerable impact, with a 75% reduction in deaths among children from 2000 to 2012 (Simons et al., 2012).

EPIDEMIOLOGY AND TRANSMISSION: Measles is highly contagious among vaccine controlled and immunizable diseases, having estimated reproduction rate (R0) between 12 to 18. This implies that an infected human can potentially spread the disease to 12 to 18 other humans if they all have close contact and are susceptible to the virus (Plotkin, 2013). Measles has a secondary attack rate of over 90% in individuals who are susceptible. The Measles virus can spread through the air via respiratory droplets that are aerosolized, through indirect or direct contact with infected individuals' throat and nasal secretions when they cough, sneeze, or breathe (Centers for Disease Control and Prevention, 2014). The viral surface protein haemagglutinin attaches to host cell receptors, including nectin 4 (PVRL4), signalling lymphocytic activation molecule (CD150) and cofactor protein of human membrane (CD46) (Bhattacharjee & Yadava, 2018). Since the start of the year 2019, there have been 704 confirmed cases of measles in the United States, according to CDC data from April 26, 2019. The country has had the biggest increase in measles cases reported in a single year since 963 cases were reported in 1994 and the measles was declared eradicated in 2000. (Patel et al., 2019).

DIAGNOSIS: Measles is classified as an infection that affects the entire body. After being exposed to the virus, it takes about 10-12 days for the first symptoms to appear. Before the rash appears, there are early symptoms called "3Cs" which include cough, conjunctivitis and coryza. A high fever that could reach 105 °F is also present during the prodromal phase. Small spots with white or bluish-white centers surrounded by redness on the inner cheek around the second molar called Kopik Spots are highly specific but temporary and are seen in only 50-70% of patients (Abad & Safdar, 2015). The appearance of rash occurs around 14 days following exposure to the virus (range 7-18 days) (Smith, 2022). The following criteria can be used to confirm measles virus infection in a laboratory setting:

·         Measles virus extraction from urine, conjunctival swabs, nasopharyngeal secretions or blood mononuclear cells

·         Serological test: antibody test for measles-specific immunoglobulin M (IgM)

·         A significant increase of four times or more in the levels of measles-specific IgG antibodies between convalescent sera and acute sera

·         Using reverse transcriptase-polymerase chain reaction (RT-PCR) to detect measles virus RNA in throat, nose, blood, urine and nasopharyngeal samples (Kobaidze & Wallace, 2017).

The most commonly utilized laboratory technique for verifying measles virus infection is measles-specific serological testing of IgM antibody  (Moss, 2017).

TREATMENT: Measles, similar to other viral infections, is managed through supportive care. No antiviral treatment specifically targets measles. However, for children with severe cases of measles, the World Health Organization (WHO) advises the provision of vitamin A including those who are hospitalized (Organization, 2022). It is recommended to give children who have acute measles a daily oral dose of vitamin A for two days in a row. According to the child's age, the recommended dose of vitamin A is 50,000 IU for newborns under six months, 100,000 IU for infants between six and eleven months, and 200,000 IU for children over twelve months (Lindberg et al., 2015).

ACTIVE IMMUNIZATION: The discovery of the measles vaccine is considered to be an extremely cost-effective health measure. Before the measles vaccine was introduced, measles caused over 2 million deaths globally each year (Kumar & Sabella, 2016). The incidence of measles has significantly decreased in the past two decades, and as a result of the high use of weakened measles vaccines, the number of deaths associated with measles has decreased to just over 100,000 in 2015 (Moss, 2017). In order to eradicate measles, vaccination rates in the population must be over 93% (A. K. Leung et al., 2018). It is recommended to universally vaccinate all vulnerable persons, including children with the measles vaccine (Organization, 2019). The live, weakened measles strains in current vaccines reproduce inside the body of the recipient, inducing humoral and cellular immunity (Sood et al., 2017). If the measles vaccine is administered as a single dose when an individual reaches or surpasses the age of one year, its protection against measles is around 93% to 95% . However, when 2 doses of the vaccine are given at appropriate intervals, the effectiveness increases to nearly 100%. In contrast, administering the measles vaccine at the age of 9 months provides only 85% protection and these vaccines are typically administered in combination with other vaccines, such as the MMRV and MMR vaccine (Bester, 2016).

POSTEXPOSURE PROPHYLAXIS: Giving measles vaccination to individuals who have been exposed to the virus and are susceptible within 72 hours after exposure can effectively halt or reduce the intensity of disease. This is the preferred method over the use of immunoglobulin (Organization, 2019). Those persons who have no evidence of immunity to measles may receive the measles-containing vaccine as a preventive measure after exposure (postexposure prophylaxis) , except for pregnant women and those with weakened immune systems. (Martinez et al., 2018).

DISEASE PREVENTION AND CONTROL: Individuals who may be susceptible to contracting measles are advised to avoid attending school or work during the period of 5 to 21 days following their most recent exposure to the virus. If they are given prophylactic immunoglobulin, they should extend their absence to 28 days. Uncomplicated cases of measles that have been confirmed can typically be treated at home (Kobaidze & Wallace, 2017). It is important to emphasize proper hand washing technique (Bentley et al., 2014).

CYTOMEGALOVIRUS: A global infectious virus, Human cytomegalovirus belonging to class Herpesviridae is an agent of enhanced differences in seroprevalence exist between countries (Styczynski, 2018).This ubiquitous virus pathogen is never cleared from host body. It has been innocuous in immunocompetent patients but cause severe complications in immunocompromised patients including blindness, end organ disease, also death in newborns (Vasilieva, Gianella and Freeman, 2020)

            

 HIGH RISK PATIENTS: Mostly patients with high exposure of CVM disease including:

·         Neonates because of their immature immune system development.

·         Patients with primary and secondary immunodeficiencies caused by hematological malignancies such as human immunodeficiency virus (HIV) and systemic leukemia.

·         Patients with compromised kidney receptive of hemodialysis.

·         Receptive of immunosuppressive drugs: anti-tumor necrosis factor (TNF), anti-CD20, CD25 and CD52

·         Solid organ transplantation patients

·          Patients who are receptive of immunosuppressive therapies (Styczynski, 2018)

METHODS TO CURE CYTOMEGALOVIRUS

·         T-cell adoptive immunity transfer against CMV in hematopoietic stem cell transplants.

·         Second line drugs Cidofovir (CDV) and foscarnet.

·         Against viral UL97 kinase new antiviral Maribavir.

·         Large molecule therapeutics.

·         Newly approved antiviral against CMV which inhibits terminase complex is letermovir.

·         Against HCMV latency different therapies.(Krishna, Wills and Sinclair, 2019)

·         PREVENTIONS FOR CMV: After solid organ transplantation, patients who undergo immunosuppressive therapy are at high risk of various infections. Frequently CMV infection have been shown to increase morbidity and mortality in particularly shortly after transplantation. (Kanj et al., 1996)Therefore, routinely different strategies are used after solid organ transplantation (Perkins, 2007). The two preventive measures for post-transplant patients are Prophylaxis with antiviral substances and Preemptive therapy(Simon et al., 2016).
description: CORONAVIRUS: The newly discovered Corona virus is the cause for the pandemic that began in December 2019 and emerged from Wuhan. SARS-COV-2, a pathogenic virus that causes Corona-virus disease 2019 (COVID-19) and is the cause of the continuing pandemic affecting more than 210 countries, is a member of the beta corona virus genera of the Coronaviridiae family (Abid et al., 2020).

Corona-virus is an enveloped RNA (ribonucleic acid) virus that has a diameter of 60 to 140 nm. Its name, "corona virus," comes from the way it resembles a crown. Coronaviruses are positive single-stranded, enclosed, big RNA viruses that can infect a variety of animals in addition to humans. By isolating the viruses from cold patients, Tyrell and Bynoe published the first description of coronaviruses in 1966. There are four subfamilies of coronavirus, namely alpha‐, beta‐, gamma‐ and delta‐coronaviruses exist. Among the seven subtypes of coronaviruses that can infect humans, the beta‐coronaviruses may cause severe disease and fatalities, whereas alpha‐coronaviruses cause asymptomatic or mildly symptomatic infections. SARS- CoV‐2 belongs to the B lineage of the beta‐coronaviruses and is closely related to the SARS‐ C0VID virus.

There are major four structural genes encode nucleocapsid protein (N), the spike protein (S), a small membrane protein (SM) and the membrane glycoprotein (M) with an additional membrane glycoprotein (HE) occurring in the HCoV‐OC43 and HKU1 beta‐ coronaviruses (Cascella et al., 2022).

Coronavirus was declared pandemic as the sixth public health emergency of international concern( PHEIC)  by WHO on March 11, 2020 (Abid et al., 2020).

TRANSMISSION: SARS‐CoV‐2 pandemic has making its transition from animals to humans on the Huanan seafood market in Wuhan, China; The virus that causes COVID-19 is mainly transmitted through tiny particles generated when diseased person coughs, sneezes, or respires. These droplets are too weighty to suspend in the air, and rapidly drop on floors (Cascella, Rajnik et al. 2022).

DIAGNOSIS:

POLYMERASE CHAIN REACTION AND SEROLOGY: For the detection and diagnosis of SARS-CoV-2 RNA RT PCR based test are standard test for detection. Moreover, the sensitivity of testing differs with timing of test and comparative to the contact.

Numerous serological tests can also provide assistance in the diagnosis and measurement of responses to novel vaccines.

Accessible serological assays comprise point-of-care assays and high throughput enzyme immunoassays. Morever, test performance, accuracy, and validity are variable. (Wiersinga et al., 2020).

PREVENTIVE MEASURES: Some of these preventive measures are given below:

·         High standard of personal hygiene. This involves constant hand washing using soap and water for up to 20 seconds particularly after visiting a public place (Riaz et al., 2022).

·         People who directly involved in testing and exposure of virus make sure the implementation of SOPs.

·         Positive cases should be separated from the community. 

·         After the travel or return take a quarantine period of 14 days.

·         Check carefully the imports and exports to stop the transmission of virus in the community. (Kirtipal et al., 2020).

·         Make sure the cases are fully recovered before discharge from the hospital

·         Avoid stigmatization. Stigmatization could be awkward thus stopping likely infected persons from screening for the test and following isolation (Choi, 2020).

·         Immune response can be improved by eating fruits and vegetables along with healthy.

TREATMENT: There are the few classes of drugs are being used for the management of COVID-19: antivirals (eg, remdesivir, favipiravir), antibodies (eg, convalescent plasma, hyperimmune immunoglobulins), antifibrotics (eg, tyrosine kinase inhibitors), anti-inflammatory agents (dexamethasone, statins), (eg, heparin), and targeted immunomodulatory therapies (eg, tocilizumab, sarilumab, anakinra, ruxolitinib), anticoagulants. It is also observed that different kind of medicines are useful for different personals (Wiersinga et al., 2020).

There are few other beneficial approaches consist of moderating the inflammatory response in patients with COVID-19. Monoclonal antibodies directed against key inflammatory mediators, such as interferon gamma, interleukin 1, interleukin 6, and complement factor 5a, all target the overwhelming inflammatory response following SARS-CoV-2 infection with the goal of preventing organ damage (Wiersinga et al., 2020).

VACCINE: COVID-19 vaccines are a critical tool in the fight against the COVID-19 pandemic. As of my knowledge cutoff in September 2021, there were several COVID-19 vaccines available globally (Mistry et al., 2022). Pfizer-BioNTech COVID-19 vaccine: This vaccine uses messenger RNA (mRNA) technology to teach cells how to make a harmless piece of the spike protein found on the surface of the SARS-CoV-2 virus. Once the protein is made, the immune system recognizes it as foreign and produces antibodies against it (Angeli et al., 2021).

Moderna COVID-19 vaccine: Similar to the Pfizer-BioNTech vaccine, this vaccine uses mRNA technology to instruct cells to make the spike protein and trigger an immune response (Kumar et al., 2021).

There are different other vaccines are also used.

WEST NILE VIRUS : West Nile virus (WNV) in people could be resulted in serious neuroinvasive illnesses like encephalitis, meningitis, and even death. The possibility of having neurological disorders that are fatal and life-threatening is higher in the elderly, immunocompromised people, and people who possess specific hereditary conditions. WNV was formerly a virus that only existed in the old world, but it has now spread to the rest of the world, producing recurrent outbreaks and increasing the number of people who have neuroinvasive consequences (Sun, H et al., 2023).

TRANSMISSION: Mosquito bite is the main method of transmission of WNV to human. When the mosquitoes feed on diseased birds, they received virus and become infected. By the biting of these infected mosquitoes   humans and other animals carry the West Nile virus (Ulmen et al., 2023).

DIAGNOSIS 

·         Nucleic acid based test for West Nile Virus

·         WNV antigen detection

·         Serological diagnosis of WNV infection

CONTROL STRATEGIES

THERAPEUTICAL TREATMENT: Anti-glycine receptor antibodies were found to be present in an individual who had West Nile Virus infection and autoimmune encephalitis. The signs and symptoms of encephalitis disappeared with corticosteroid and intravenous immunoglobulin combination therapy. Some sequence similarities between viral antigens and receptor sequence fragments were discovered by in silico analysis, which points to a molecular mimicry autoimmunization mechanism (Arcilla et al., 2023).

VACCINATION: Although there is presently no vaccine for humans, there are a few licensed WNV vaccines for horses. Fort Dodge Animal Health, a current Pfizer affiliate, created the first licensed vaccination. It includes a complete, formalin-inactivated West Nile virus. The West Nile-Innovator® vaccine is currently available for purchase in the USA and is extremely efficient. In fact, protection against viremia noticed in 94% of animals   after receiving the 2 doses of West Nile-Innovator® in the challenge of twelve months. Less than 5% of   horses in a safety testing for the vaccine experienced negative side effects. Another dead viral vaccine was created by Boehringer Ingelheim (Vetera® WNV vaccine).  A vetmedica licence was aslso granted by the agriculture department of  the Unite State (De Filette et al.,  2012). A technique (ChimeriVax) can be used to create vaccines against all flaviviruses, and treatments for dengue and Japanese encephalitis, which is closely related to West Nile encephalitis, are currently in clinical trials or very close to it. Yellow fever 17D, since it is both safe and effective vaccination against the prototypical flavivirus which is employed as a live vector in ChimeriVax vaccines. The target virus's relevant genes are swapped for the yellow fever 17D vaccine's pre membrane and the enveloped protein genes utilising infectious cloning technology like in the case of west nile. The resultant chimeric virus possesses the antigens required for West Nile immunity as well as the ability to replicate yellow fever 17D. Applications for the ChimeriVax technology include speedy development of a West Nile vaccine and clinical trials (Monath et al., 2006).

VECTOR CONTROL STRATEGIES: Risk of WNV infection can be reduced by controlling the vectors. By using integrated pest management techniques, mosquito repellent sprays, organophosphates   and through proper cleaning of the areas where animals present to avoid the spread of mosquitoes.

EBOLA VIRUS:

INTRODUCTION: Filoviruses (Ebola and Marburg) are considered as the leading cause of hemorrhagic fever in humans along with apes, chimpanzees and other primates. The hemorrhagic disease of viral origin is a critical medical implication with an increase percentage of transience rate is considered due to the connection of multi-system along with its capability to weaken the vascular system, therefore causing several blood draining complications, finally the chief source of hemorrhagic fever. The Global health concerned organization known as “World Health Organization (WHO)” announced a public emergency along with the collaboration of all international health advisors on the outbreak of Ebola virus disease in Western Africa on August 8, 2014 (Briand et al., 2014), pointing the dire need of global community to control this lethal outbreak.

Members of the family Filoviridae are encased virions with non-segmented linear negative stranded RNA; having the filamentous shape, comprising the genomic size of 15-19 Kb. Various filoviruses which includes Ebola virus are lethal to people hence having a high  state of virulence as well. However, various viruses of the family filoviridae infects the bats for example, the Marburg virus. However, the origin of the hosts for the filoviruses are not yet known (Family: Filoviridae | ICTV, n.d.). Ebola viruses are the negative stranded RNA viruses and prevalent in the west and equatorial Africa. These agents associated with severe pathogenesis, with  high fatality rate and systematic ailments in humans and Apes respectively (Malvy et al., 2019). Due to its high virulence and rapid transmission capability, the Ebola virus (EBOV) lies under “Class A” bioweapon organism (Balmith et al., 2017); hence making it under regular monetization and check out of its connectivity with regular cases.

EPIDEMIOLOGY: The Ebola virus 2014 outburst in western Africa is considered as the biggest epidemic of Ebola virus disease (EVD) in the past (Team, 2014). Presently, around 12 distinct filoviruses have been described (Kuhn et al., 2019). The epidemic potential of Ebola Virus is significant depicted in the west African epidemic during the era of 2013 to 2016 (Lo et al., 2017). Ebola virus epidemic has presented various challenges with respect to its control and treatment. Approximately 70% people in Africa have been died in this epidemic (Feldmann & Geisbert, 2011).  This outbreak was unprecedented with the affected people around 28,000, and the deaths up to 11000 (Garske et al., 2017). The economic effect of this outbreak on West Africa was nastiest. However, with adequate international support and the considerable efforts of the affected countries; lead to the initiation of control programs to this outbreak. Although, this outbreak enabled scientists to initiate various research programs into Ebola virus (EBOV) related pathology and disease diagnosis pursing and leading towards effective treatment. The nations affected from lethal Ebola virus disease since 1976-2016 are illustrated in the figure 1 (Singh et al., 2017).

PATHOGENESIS &TRANSMISSION: Biosafety level-4 pathogen i-e Ebola virus demands distinct control procedures along with the protection of health-care workforces in particular. The survival of the very virus is favourable in dried and wet(liquid) constituents for days  (Piercy et al., 2010). Inactivation of these viruses incorporate the procedure of gamma (γ) irradiation of heating around 60 minutes at about 60⁰C (Celsius) or by boiling for 5 minutes. The sensitivity of the Ebola virus to bleach (sodium hypochlorite) is seen, however, they are also supplementary to detergents as well (RANGE). Whereas, refrigeration or freezing will not inactivate the Ebola virus. 

Transmission of Ebola Virus (EBOV) in humans is mainly due to direct contact of blood, skin or various bodily fluids of the patients already effected with Ebola virus disease (Rewar & Mirdha, 2014). Direct exposure to the infectious material in contrast to indirect contact; causes the significantly high threat of contagion. The virus particles with the potential of causing infection is protein coated and persist on inorganic planes; may survive several days leading up to weeks. However, they can also persist quite longer in various circumstances like controlled environmental locales like hospitals (Fischer et al., 2015). During 2014-15 epidemic in Sierra Leone, transmissions up to 74% were among household members or amongst the nearest (cousins) family members, following with 18% of transmissions through friendly circle along with other societal acquaintances. However, 8% of transmission of Ebola virus were acquired in the vicinity of hospitals (Cent. Dis. Control Prev. 2016). Furthermore, secondary contact cases may rarely exceeded up to 10-15% (Feldman HAS and Geisbert TW., 2013). The virus is also transmitted by direct interaction with the blood of an infected individual ‘s exudations, tissues, several organs along with other bodily fluids of both the living and deceased infested person (Bausch et al., 2007).

NOVEL TECHNIQUE: PRODUCTION OF ANTI-VIRAL MOLECULES FOR TREATMENT OF EBOLA VIRUS: Since Ebola virus is considered as the causative agents of fatal outbursts of the deadliest hemorrhagic fever for more than thirty years, present curative possibilities for infested personnel are restricted. Presently, there are no approved medications or vaccines for Ebola Virus (EBOV) anywhere around the globe. Modern investigative studies towards the production of any treatment of Ebola virus suggests the use of monoclonal antibodies, novel small molecule anti-viral agents, plasma transfusions from recovering patients and vaccines (Roth, 2014). Whereas, various medicines which are not known as antivirals have shown significant activity against Ebola virus both in vivo and in vitro respectively. Couple of treatments involving the use of monoclonal antibody are likely to be permitted for the practice in infected persons against the filovirus (Ebola virus). Whereas, studies on non-human primates at preclinical level depicted that several other monoclonal treatments are more potent against several other species of filoviruses. A distinct advancement is seen in terms of small antiviral molecules and host-targeted tactics (Bradfute, 2022)
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CON NOVEL STRATEIES TO CONTROL EXISTING AND EMERGING VIRAL DISEASES:

There are several novel strategies to control viral diseases that have shown promising results in recent years.

·         Vaccines: Vaccines are one of the most effective ways to prevent viral diseases. For example Rotavirus mortality has decreased with time because of the rotavirus vaccine introduction in children (Troeger et al., 2018).

·         Antiviral drugs: Antiviral drugs target specific viral enzyme and specific proteins to inhibit viral replication. For example Remdesivir is a broad-spectrum antiviral agent, emerged as candidate drug for treatment of novel coronavirus 2019 (COVID-19) (Lamb, 2020).

·         Gene editing: Gene editing technologies CRISPR-Cas9 based good manufacturing practice (GAP)-compliant protocol that targets and knocks out the gene for adaptor protein functions of tacrolimus, this was done by transient delivery of ribonucleoprotein complexes into CMV-specific T-cells (Amini et al., 2021).

·         Passive immunization: Passive immunization involves the administration of preformed antibodies to individuals after post-exposure (Saphire et al., 2018).

·         RNA interference (RNAi): RNAi involves the use of small interfering RNAs (siRNAs) to silence viral gene and prevent viral replication. This strategy has shown potential of controlling viruses like West Nile Virus (Krishnan et al., 2008).

·         Convalescent plasma therapy: In convalescent plasma therapy we transfuse plasma from recovered individuals to those who are exposed with infection and sick. This strategy was used to treat COVID-19 (Rajendran et al., 2020).

CONCLUSION:

Viral diseases are causing the considerable level of mortality and morbidity and are a major threat to public health. The traditional strategies, such as antiviral drugs, vaccination and host immune responses have been successful in controlling the viral diseases, but high mutation rates of viruses cause the limited efficacy of these strategies. Novel strategies, such as, nanotechnology, RNA interference (RNAi), and gene editing techniques such as CRISPR/Cas9 offer promising methods in controlling the viral diseases. However, there are still further research is needed to get a complete understanding of the efficacy, safety and practical applications of these strategies to treat the viral diseases. Researchers can mitigate the global impact of viral infections by continuing the development of novel strategies to combat and control the existing and emerging viral diseases.

 





 


















 

 

 
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