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

The 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 eighty-four natural compounds from Peruvian sources against different mutations on the Mpro target. Using computational technics, we applied virtual screening, all-atom molecular dynamics simulations, and binding free energy estimation by MM/GBSA methods. 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. Our results demonstrated the antiviral capacity of compounds from Peruvian sources against SARS-CoV-2 Mpro and its mutations, which could significantly prevent and treat SARS-CoV-2 infection.