New insights into the catalytic mechanism of the SARS-CoV-2 main protease: an ONIOM QM/MM approach.

ABSTRACT: SARS-CoV-2 M^pro, also known as the main protease or 3C-like protease, is a key enzyme involved in the replication process of the virus that is causing the COVID-19 pandemic. It is also the most promising antiviral drug target targeting SARS-CoV-2 virus. In this work, the catalytic mechanism of M^pro was studied using the full model of the enzyme and a computational QM/MM methodology with a 69/72-atoms QM region treated at DLPNO-CCSD(T)/CBS//B3LYP/6-31G(d,p):AMBER level and including the catalytic important oxyanion-hole residues. The transition state of each step was fully characterized and described together with the related reactants and products. The rate-limiting step of the catalytic process is the hydrolysis of the thioester-enzyme adduct, and the calculated barr

SUBMITTER: Fernandes HS 

PROVIDER: S-EPMC8224256 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature