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Curr Pharm Des ; 27(32): 3490-3500, 2021.
Article in English | MEDLINE | ID: covidwho-1024456


BACKGROUND: The unusual pneumonia outbreak that originated in the city of Wuhan, China in December 2019 was found to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19. METHODS: In this work, we have performed an in silico design and prediction of potential siRNAs based on genetic diversity and recombination patterns, targeting various genes of SARS-CoV-2 for antiviral therapeutics. We performed extensive sequence analysis to analyze the genetic diversity and phylogenetic relationships, and to identify the possible source of virus reservoirs and recombination patterns, and the evolution of the virus as well as we designed the siRNAs which can be used as antivirals against SARS-CoV-2. RESULTS: The sequence analysis and phylogenetic relationships indicated high sequence identity and closed clusters with many types of coronavirus. In our analysis, the full-genome of SARS-CoV-2 showed the highest sequence (nucleotide) identity with SARS-bat-ZC45 (87.7%). The overall sequence identity ranged from 74.3% to 87.7% with selected SARS viruses. The recombination analysis indicated the bat SARS virus is a potential recombinant and serves as a major and minor parent. We have predicted 442 siRNAs and finally selected only 19 functional, and potential siRNAs. CONCLUSION: The siRNAs were predicted and selected based on their greater potency and specificity. The predicted siRNAs need to be validated experimentally for their effective binding and antiviral activity.

COVID-19 , SARS-CoV-2 , Antiviral Agents/pharmacology , Computer Simulation , Humans , Phylogeny , RNA, Small Interfering/genetics
Vaccines (Basel) ; 8(4)2020 Nov 01.
Article in English | MEDLINE | ID: covidwho-902683


The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 and causes severe and often fatal acute respiratory illness in humans. No approved prophylactic and therapeutic interventions are currently available. In this study, we have developed egg yolk antibodies (immunoglobulin Y (IgY)) specific for MERS-CoV spike protein (S1) in order to evaluate their neutralizing efficiency against MERS-CoV infection. S1-specific immunoglobulins were produced by injecting chickens with purified recombinant S1 protein of MERS-CoV at a high titer (5.7 mg/mL egg yolk) at week 7 post immunization. Western blotting and immune-dot blot assays demonstrated that the IgY antibody specifically bound to the MERS-CoV S1 protein. Anti-S1 antibodies were also able to recognize MERS-COV inside cells, as demonstrated by an immunofluorescence assay. Plaque reduction and microneutralization assays showed the neutralization of MERS-COV in Vero cells by anti-S1 IgY antibodies and non-significantly reduced virus titers in the lungs of MERS-CoV-infected mice during early infection, with a nonsignificant decrease in weight loss. However, a statistically significant (p = 0.0196) quantitative reduction in viral antigen expression and marked reduction in inflammation were observed in lung tissue. Collectively, our data suggest that the anti-MERS-CoV S1 IgY could serve as a potential candidate for the passive treatment of MERS-CoV infection.