SRX3177, a CDK4/6-PI3K-BET inhibitor, in combination with an RdRp inhibitor, Molnupiravir, or an entry inhibitor MU-UNMC-2, has potent antiviral activity against the Omicron variant of SARS-CoV-2.

ABSTRACT: Despite considerable progress in developing vaccines and antivirals to combat COVID-19, the rapid mutations of the SARS-CoV-2 genome have limited the durability and efficacy of the current vaccines and therapeutic interventions. Hence, it necessitates the development of novel therapeutic approaches or repurposing existing drugs that target either viral life cycle, host factors, or both. Here, we report that SRX3177, a potent triple-activity CDK4/6-PI3K-BET inhibitor, blocks replication of the SARS-CoV-2 Omicron variant with IC₅₀ values at sub-micromolar concentrations without any impact on the cell proliferation of Calu-3 cells at and below its IC₅₀ concentration. When SRX3177 is combined with EIDD-1931 (active moiety of a small-molecule prodrug Molnupiravir) or MU-UN

SUBMITTER: Pandey K 

PROVIDER: S-EPMC11922097 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature