High-throughput screening and characterization of novel inhibitors targeting HIV-1 protease precursor autoprocessing.

ABSTRACT: HIV-1 protease (PR) is initially synthesized as part of the Gag-Pol polyprotein precursor, which undergoes temporospatially regulated autoprocessing to liberate mature PR. The free mature enzyme is the target of currently available protease inhibitors (PIs). To explore alternative therapeutic strategies, we developed a cell-based high-throughput screening (HTS) platform targeting precursor autoprocessing, screened approximately 320,000 small molecules, and identified 27 compounds that partially suppress precursor autoprocessing. A highly sensitive infectivity assay confirmed that several compounds inhibited viral infectivity in a dose-dependent manner, with EC₅₀ values in the low micromolar range. Notably, hit compound C7 exhibited comparable potency against both wild-type and d

SUBMITTER: Jeep RH 

PROVIDER: S-EPMC12511561 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature