9-aminominocycline potentiates the efficacy of EIDD-1931 and PF-332 by targeting the papain like protease enzyme of SARS-CoV-2.

ABSTRACT: The 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp) are key enzymes in SARS-CoV-2 replication and serve as critical targets for an antiviral drug. Currently, Paxlovid® and Lagevrio™ specifically target 3CLpro and RdRp, respectively, for COVID-19 treatment. However, no antivirals target for the SARS-CoV-2 PLpro enzyme, essential for viral replication and suppression of the host antiviral immune response. This study identified 9-aminominocycline (9-AMN) as a potent inhibitor of SARS-CoV-2 PLpro. Unlike the parent compound minocycline, 9-AMN inhibits PLpro's proteolytic and deubiquitinase activities by approximately 90%, with IC₅₀ values of 4.15 µM and 4.55 µM, respectively, while showing no effect on the enzymatic activi

SUBMITTER: Pandey K 

PROVIDER: S-EPMC11830066 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature