Identification of Potential Inhibitors of SARS-CoV-2 Main Protease via a Rapid In-Silico Drug Repurposing Approach

Cesar Mendoza-Martinez, Alejandro Rodriguez-Lezama

10.26434/chemrxiv.12085083.v1

Research curated

Abstract

An in-silico drug repurposing study was carried out to search for potential COVID-19 antiviral agents. A dataset of 1615 FDA-approved drugs was docked in the active site of SARS CoV-2 Main protease. A subset of the top scoring hit compounds was subjected to follow-up molecular dynamics simulations to further characterise the predicted binding modes. The main findings are that the drugs Aliskiren, Capreomycin, Isovuconazonium, emerge as novel potential inhibitors. We also observed that Ceftolozane, Cobicistat, Carfilzomib and Saquinavir are well-ranked by our protocol, in agreement with other recent in silico drug repurposing studies, however MD simulations shows only potential for the three first, as Saquinavir exhibited an unstable binding mode. As many HIV-protease inhibitors has been reported as active and not active, Atazanavir and Lopinavir were included in the data set in order to rationalize the findings. In addition, our protocol ranked favourably Dronedarone suggesting that this recently reported SARS-CoV-2 inhibitor targets SARS-CoV-2 Main protease.

Source: ChemRxiv

Related molecules

Name	Synonyms	Genes
Aliskiren
Isavuconazonium sulfate
Ceftolozane
Cobicistat
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Capreomycin	Capastat
Carfilzomib

Related interactions

Target	Drug	Type	Result
3C-like protease	Aliskiren	Computational	positive
3C-like protease	Isavuconazonium sulfate	Computational	positive
3C-like protease	Ceftolozane	Computational	positive
3C-like protease	Cobicistat	Computational	positive
3C-like protease	Capreomycin	Computational	positive
3C-like protease	Carfilzomib	Computational	positive