Identification of compounds from natural Peruvian sources as potential inhibitors of SARS-CoV-2 Mpro mutations by virtual screening and computational simulations

Abstract

Background The coronavirus disease (COVID-19) pandemic continues to be a public health problem worldwide. Several therapeutic targets of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified, whereas the main protease (Mpro) is necessary for virus replication. Since SARS- CoV-2 Mpro mutation rates are inherently high, searching for new inhibitors remains challenging. Herein, this work aimed to evaluate 84 natural compounds from Peruvian sources against different mutations on the Mpro target. Methods We applied virtual screening, all-atom molecular dynamics simulations, and binding free energy estimation by Molecular Mechanics/Generalized Born Surface Area (MM/GBSA). Results The virtual screening results helped us identify rutin as the top compound against different Mpro mutations. Likewise, the computational simulations demonstrated the high structural stability of the Mpro-rutin system. Conclusions his research evaluated the antiviral capacity of Peruvian sources against SARS-CoV-2 Mpro and its mutations, which could be important in preventing and treating SARS-CoV-2 infection.