Inhibitor binding influences the protonation states of histidines in SARS-CoV-2 main protease.

ABSTRACT: The main protease (M^pro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an attractive target for antiviral therapeutics. Recently, many high-resolution apo and inhibitor-bound structures of M^pro, a cysteine protease, have been determined, facilitating structure-based drug design. M^pro plays a central role in the viral life cycle by catalyzing the cleavage of SARS-CoV-2 polyproteins. In addition to the catalytic dyad His41-Cys145, M^pro contains multiple histidines including His163, His164, and His172. The protonation states of these histidines and the catalytic nucleophile Cys145 have been debated in previous studies of SARS-CoV M^pro, but have yet to be investigated for SARS-CoV-2. In this work we have used molecular

SUBMITTER: Pavlova A 

PROVIDER: S-EPMC8899719 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature