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

Abhik Kumar Ray, Parth Sarthi Sen Gupta, Saroj Kumar Panda, Satyaranjan Biswal, Malay Kumar Rana

10.26434/chemrxiv.12278066.v1

Research curated

Abstract

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.

Source: ChemRxiv

Related molecules

Name	Synonyms	Genes
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Velpatasvir
Glecaprevir	Glecaprevir , UNII-K6BUU8J72P , ABT-493 , 1365970-03-1 , K6BUU8J72P

Related interactions

Target	Drug	Type	Result
3C-like protease	Velpatasvir	Computational	positive
3C-like protease	Glecaprevir	Computational	positive