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Repurposing of FDA Approved Drugs for the Identification of Potential Inhibitors of SARS-CoV-2 Main Protease

preprint
revised on 12.05.2020 and posted on 14.05.2020 by Abhik Kumar Ray, Parth Sarthi Sen Gupta, Saroj Kumar Panda, Satyaranjan Biswal, Malay Kumar Rana

COVID-19, responsible for several deaths, demands a cumulative effort of scientists worldwide to curb the pandemic. The main protease, responsible for the cleavage of the polyprotein and formation of replication complex in virus, is considered as a promising target for the development of potential inhibitors to treat the novel coronavirus. The effectiveness of FDA approved drugs targeting the main protease in previous SARS-COV (s) reported earlier indicates the chances of success for the repurposing of FDA drugs against SARS-COV-2. Therefore, in this study, molecular docking and virtual screening of FDA approved drugs, primarily of three categories: antiviral, antimalarial, and peptide, are carried out to investigate their inhibitory potential against the main protease. Virtual screening has identified 53 FDA drugs on the basis of their binding energies (< -7.0 kcal/mol), out of which the top two drugs Velpatasvir (-9.1 kcal/mol) and Glecaprevir (-9.0 kcal/mol) seem to have great promise. These drugs have a stronger affinity to the SARS-CoV-2 main protease than the crystal bound inhibitor α-ketoamide 13B (-6.7 kcal/mol) or Indinavir (-7.5 kcal/mol) that has been proposed in a recent study as one of the best drugs for SARS-CoV-2. The in-silico efficacies of the screened drugs could be instructive for further biochemical and structural investigation for repurposing. The molecular dynamics studies on the shortlisted drugs are underway.

Funding

None

History

Email Address of Submitting Author

mrana@iiserbpr.ac.in

Institution

Indian Institute of Science Education and Research (IISER) Berhampur

Country

India

ORCID For Submitting Author

0000-0002-1713-8220

Declaration of Conflict of Interest

The authors report no conflicts of interest.

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