Abstract
BackgroundThe Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) outbreak originating in Wuhan, China, has raised global health concerns and the pandemic has now been reported on all inhabited continents. Hitherto, no antiviral drug is available to combat this viral outbreak.MethodsKeeping in mind the urgency of the situation, the current study was designed to devise new strategies for drug discovery and/or repositioning against SARS-CoV-2. In the current study, RNA-dependent RNA polymerase (RdRp), which regulates viral replication, is proposed as a potential therapeutic target to inhibit viral infection.ResultsEvolutionary studies of whole-genome sequences of SARS-CoV-2 represent high similarity (> 90%) with other SARS viruses. Targeting the RdRp active sites, ASP760 and ASP761, by antiviral drugs could be a potential therapeutic option for inhibition of coronavirus RdRp, and thus viral replication. Target-based virtual screening and molecular docking results show that the antiviral Galidesivir and its structurally similar compounds have shown promise against SARS-CoV-2.ConclusionsThe anti-polymerase drugs predicted here—CID123624208 and CID11687749—may be considered for in vitro and in vivo clinical trials.
Highlights
The Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) outbreak originating in Wuhan, China, has raised global health concerns and the pandemic has been reported on all inhabited continents
Homology modeling and protein phylogenetic analysis RNA-dependent RNA polymerase (RdRp) protein amino acids (AA) from severe acute respiratory syndrome (SARS)-CoV and SARS-CoV-2 were aligned with the help of Clustal X 2.1 software using default parameters, and the sequences were further refined by GeneDoc to find the similarity between them
Most of the accessions in clade I belong to the Betacoronaviruses, indicating they all are closely related to each other, while only one and two accessions belong to alpha-CoV and gamma-CoV, respectively, thereby representing some distance with respect to the Betacoronavirus members
Summary
The Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) outbreak originating in Wuhan, China, has raised global health concerns and the pandemic has been reported on all inhabited continents. Two SARS strains have been reported to cause epidemics: (1) SARS-CoV, identified in 2002–2004, and (2) SARS-CoV-2, known as the novel coronavirus that emerged as a potential threat in late 2019 [6] Both these strains evolved from a common Betacoronavirus ancestor; it is believed that SARS-CoV-2 first infected humans from a bat host during interspecies viral transmission. In support, it has been reported in China and other countries that bats are the primary reservoirs of SARS-CoV-2 [6,7,8].
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