An insight into the interaction between α-ketoamide- based inhibitor and coronavirus main protease: A detailed in silico study.

ABSTRACT: The search for therapeutic drugs that can neutralize the effects of COVID-2019 (SARS-CoV-2) infection is the main focus of current research. The coronavirus main protease (M_pro) is an attractive target for anti-coronavirus drug design. Further, α-ketoamide is proved to be very effective as a reversible covalent-inhibitor against cysteine proteases. Herein, we report on the non-covalent to the covalent adduct formation mechanism of α-ketoamide-based inhibitor with the enzyme active site amino acids by QM/SQM model (QM = quantum mechanical, SQM = semi-empirical QM). To uncover the mechanism, we focused on two approaches: a concerted and a stepwise fashion. The concerted pathway proceeds via deprotonation of the thiol of cysteine (here, Cys₁₄₅ SγH) and simultaneous rever

SUBMITTER: Banerjee S 

PROVIDER: S-EPMC7695570 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature