In Silico Research of New Potent SARS Cov-2 Main Protease Inhibitors

Abstract

The covid-19 pandemic caused by SARS-CoV-2 virus has caused more than 5.3 million deaths worldwide since the beginning of 2020. Although there is no specific drug against SARS-CoV-2 until now, studies are daily progressing to find new drugs to eradicate this virus.
In this study we propose new microbial inhibitors of the main protease which represents a therapeutic target of SARS-CoV-2, by the simulation in silico the affinity of 68 compounds extracted from the literature towards the Mpro by using molecular Docking.
This method consists in predicting the protein-ligand interaction mode by Flexx, it’s   among the most used programs in this approach. We propose new Mpro inhibitors using Molecular Docking by taking as starting structure the ligand N3 of the base complex 6LU7. The Molecular Docking of the 35 microbial compounds selected with regard to the active site of Mpro highlights compounds Ammonificin C (S1), Pityriacitrin E (S2) and Kaempferol compound (S3) as the best inhibitors of this enzyme with respective interaction energies of -36.16 kJ/mol, -28.38 kJ/mol and -27.01 kJ/mol, which exceed that of reference N3 (-15.30 kJ/mol). The predictive study of the physicochemical and pharmacokinetic properties of the compounds (S1), (S2) and (S3), showed that these compounds have good ADME profiles, and they can be proposes as new potentials inhibitors against the Mpro of SARS-CoV-2.
This study reveals the importance of bioinformatics tools in the rapid development of therapeutic molecules and also highlights the antiviral potentialities of microbial metabolites and their ability to be promising drug candidates.