Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR

In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.PMID:38627462 | DOI:10.1038/s41401-024-01282-z
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Source Type: research