Towards potential inhibitors of COVID-19 main protease Mpro by virtual screening and molecular docking study

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 has started in December 2019 in Wuhan, China, and become a global health problem. The SARS-COV-2 main protease (Mpro) play a crucial role in the multiplication and control of virus activity. Therefore, we assume that the inhibition of these enzymes inhibits viral replication. To determine potential inhibitors of this protease among existing chemical libraries, we have carried out a virtual screening of 300 antiviral molecules obtained by the ASINEX database. Nine molecules were chosen based on their stability with the target (Mpro), and the molecular docking study was carried out against the same target. These molecules showed higher binding affinities than the positive control to the active site of the same target (Mpro) and exhibit interactions with the amino acids responsible for the inhibitory activity of this enzyme (Cys145 and His 41). Then, these molecules were selected and chosen as potential inhibitors of SARS-Cov-2. Highlights Three hundred antiviral compounds obtained from the ASINEX database were subjected to a virtual screening against SARS-COV-2 main protease Mpro. Nine molecules were selected and were subjected to molecular docking against the same target to evaluate their stability and the mode of binding inside the active site. The nine molecules show favourable interactions with the two amino acids Cys145 and His41, which suggests that these molecules could have competitive inhibitory activity. against the Mpro target main protease The graphical abstract was created using BioRender.com.