Why is the Omicron main protease of SARS-CoV-2 less stable than its wild-type counterpart? A crystallographic, biophysical, and theoretical study of the free enzyme and its complex with inhibitor 13b-K.

ABSTRACT: During the continuing evolution of SARS-CoV-2, the Omicron variant of concern emerged in the second half of 2021 and has been dominant since November that year. Along with its sublineages, it has maintained a prominent role ever since. The Nsp5 main protease (M^pro) of the Omicron virus is characterized by a single dominant mutation, P132H. Here we determined the X-ray crystal structures of the P132H mutant (or O-M^pro) as free enzyme and in complex with the M^pro inhibitor, the alpha-ketoamide 13b-K, and we conducted enzymology, biophysical as well as theoretical studies to characterize the O-M^pro. We found that O-M^pro has a similar overall structure and binding with 13b-K; however, it displays lower enzymatic activity and

SUBMITTER: Ibrahim M 

PROVIDER: S-EPMC10942327 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature