Novel covalent and non-covalent complex-based pharmacophore models of SARS-CoV-2 main protease (M^pro) elucidated by microsecond MD simulations.

ABSTRACT: As the world enters its second year of the pandemic caused by SARS-CoV-2, intense efforts have been directed to develop an effective diagnosis, prevention, and treatment strategies. One promising drug target to design COVID-19 treatments is the SARS-CoV-2 M^pro. To date, a comparative understanding of M^pro dynamic stereoelectronic interactions with either covalent or non-covalent inhibitors (depending on their interaction with a pocket called S1' or oxyanion hole) has not been still achieved. In this study, we seek to fill this knowledge gap using a cascade in silico protocol of docking, molecular dynamics simulations, and MM/PBSA in order to elucidate pharmacophore models for both types of inhibitors. After docking and MD analysis, a set of complex-based pharmacophore

SUBMITTER: Hayek-Orduz Y 

PROVIDER: S-EPMC9386674 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature