Atazanavir Is a Competitive Inhibitor of SARS-CoV-2 M^pro, Impairing Variants Replication In Vitro and In Vivo.

ABSTRACT: Atazanavir (ATV) has already been considered as a potential repurposing drug to 2019 coronavirus disease (COVID-19); however, there are controversial reports on its mechanism of action and effectiveness as anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Through the pre-clinical chain of experiments: enzymatic, molecular docking, cell-based and in vivo assays, it is demonstrated here that both SARS-CoV-2 B.1 lineage and variant of concern gamma are susceptible to this antiretroviral. Enzymatic assays and molecular docking calculations showed that SARS-CoV-2 main protease (M^pro) was inhibited by ATV, with Morrison's inhibitory constant (K_i) 1.5-fold higher than GC376 (a positive control) dependent of the catalytic water (H₂O_cat)

SUBMITTER: Chaves OA 

PROVIDER: S-EPMC8777605 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature