Insights into the binding and covalent inhibition mechanism of PF-07321332 to SARS-CoV-2 M^pro.

ABSTRACT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been causing the COVID-19 pandemic, resulting in several million deaths being reported. Numerous investigations have been carried out to discover a compound that can inhibit the biological activity of the SARS-CoV-2 main protease, which is an enzyme related to the viral replication. Among these, PF-07321332 (Nirmatrelvir) is currently under clinical trials for COVID-19 therapy. Therefore, in this work, atomistic and electronic simulations were performed to unravel the binding and covalent inhibition mechanism of the compound to M^pro. Initially, 5 μs of steered-molecular dynamics simulations were carried out to evaluate the ligand-binding process to SARS-CoV-2 M^pro. The successfully generated bound

SUBMITTER: Ngo ST 

PROVIDER: S-EPMC8979274 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature