A potential allosteric inhibitor of SARS-CoV-2 main protease (M^pro) identified through metastable state analysis.

ABSTRACT: Anti-COVID19 drugs, such as nirmatrelvir, have been developed targeting the SARS-CoV-2 main protease, M^pro, based on the critical requirement of its proteolytic processing of the viral polyproteins into functional proteins essential for viral replication. However, the emergence of SARS-CoV-2 variants with M^pro mutations has raised the possibility of developing resistance against these drugs, likely due to therapeutic targeting of the M^pro catalytic site. An alternative to these drugs is the development of drugs that target an allosteric site distant from the catalytic site in the protein that may reduce the chance of the emergence of resistant mutants. Here, we combine computational analysis with in vitro assay and report the discovery of a potential

SUBMITTER: Fatima A 

PROVIDER: S-EPMC11413593 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature