Atomistic-Level Description of the Covalent Inhibition of SARS-CoV-2 Papain-like Protease.

ABSTRACT: Inhibition of the papain-like protease (PLpro) of SARS-CoV-2 has been demonstrated to be a successful target to prevent the spreading of the coronavirus in the infected body. In this regard, covalent inhibitors, such as the recently proposed VIR251 ligand, can irreversibly inactivate PLpro by forming a covalent bond with a specific residue of the catalytic site (Cys¹¹¹), through a Michael addition reaction. An inhibition mechanism can therefore be proposed, including four steps: (i) ligand entry into the protease pocket; (ii) Cys¹¹¹ deprotonation of the thiol group by a Brønsted-Lowry base; (iii) Cys¹¹¹-S^- addition to the ligand; and (iv) proton transfer from the protonated base to the covalently bound ligand. Evaluati

SUBMITTER: Hognon C 

PROVIDER: S-EPMC9143025 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature