Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach

• Published in: Journal of translational medicine 2020-07, Vol.18 (1), p.275-275, Article 275
• Main Authors: Aftab, Syed Ovais, Ghouri, Muhammad Zubair, Masood, Muhammad Umer, Haider, Zeshan, Khan, Zulqurnain, Ahmad, Aftab, Munawar, Nayla
• Format: Article
• Language: English
• Subjects: Active site; Amino Acid Sequence; Amino acids; Analysis; Antiviral agents; Betacoronavirus - enzymology; Betacoronavirus - isolation & purification; China; Clinical trials; Computational Biology; Computer applications; Coronaviridae; Coronavirus Infections - drug therapy; Coronavirus Infections - virology; Coronaviruses; COVID-19; Disease transmission; DNA-directed RNA polymerase; Drug development; Drug discovery; Drug Evaluation, Preclinical; Drugs; Epidemics; Evolution, Molecular; Genomes; Genomics; Health aspects; Homology modeling; Humans; Ligands; Middle East respiratory syndrome; Molecular Docking; Molecular Docking Simulation; Molecular Targeted Therapy; Nitazoxanide; Pandemics; Penciclovir; Phylogenetic tree; Phylogenetics; Phylogeny; Pneumonia, Viral - drug therapy; Pneumonia, Viral - virology; Proteins; RdRp; Replication; Respiratory diseases; RNA; RNA polymerase; RNA-Dependent RNA Polymerase - chemistry; RNA-Dependent RNA Polymerase - metabolism; RNA-directed RNA polymerase; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Sofosbuvir; Therapeutic applications; Therapeutic targets; Thermodynamics; Viruses; World health
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-020-02439-0

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 now been reported on all inhabited continents. Hitherto, no antiviral drug is available to combat this viral outbreak. Keeping 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. Evolutionary 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. The anti-polymerase drugs predicted here-CID123624208 and CID11687749-may be considered for in vitro and in vivo clinical trials.