Direct Observation of Protonation State Modulation in SARS-CoV-2 Main Protease upon Inhibitor Binding with Neutron Crystallography.

ABSTRACT: The main protease (3CL M^pro) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is an essential enzyme for viral replication with no human counterpart, making it an attractive drug target. To date, no small-molecule clinical drugs are available that specifically inhibit SARS-CoV-2 M^pro. To aid rational drug design, we determined a neutron structure of M^pro in complex with the α-ketoamide inhibitor telaprevir at near-physiological (22 °C) temperature. We directly observed protonation states in the inhibitor complex and compared them with those in the ligand-free M^pro, revealing modulation of the active-site protonation states upon telaprevir binding. We suggest that binding of other α-ketoamide coval

SUBMITTER: Kneller DW 

PROVIDER: S-EPMC8009097 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature