In silico identification of D449-0032 compound as a putative SARS-CoV-2 Mpro inhibitor

Abstract

The SARS-CoV-2 pandemic originated the urgency in developing therapeutic resources for the treatment of COVID-19. Despite the current availability of vaccines and some antivirals, the occurence of severe cases of the disease and the risk of the emergence of new virus variants still motivate research in this field. In this context, this study aimed at the computational prospection of likely inhibitors of the main protease (M^pro) of SARS-CoV-2 since inhibiting this enzyme leads to disruption of the viral replication process. The virtual screening of the antiviral libraries Asinex, ChemDiv, and Enamine targeting SARS-CoV-2 M^pro was performed, indicating the D449-0032 compound as a promising inhibitor. Molecular dynamics simulations showed the stability of the protein-ligand complex and in silico predictions of toxicity and pharmacokinetic parameters indicated the probable drug-like behavior of the compound. In vitro and in vivo studies are essential to confirm the M^pro inhibition by the D449-0032.Communicated by Ramaswamy H. Sarma.

Keywords: Mpro inhibition; SARS-CoV-2; antiviral libraries; molecular docking; molecular dynamics.