Design, synthesis, and mechanistic study of 2-piperazineone-bearing peptidomimetics as novel HIV capsid modulators.

ABSTRACT: HIV-1 capsid (CA) is an attractive target for its indispensable roles in the viral life cycle. We report the design, synthesis, and mechanistic study of a novel series of 2-piperazineone peptidomimetics as HIV capsid modulators by mimicking the structure of host factors binding to CA. F-Id-3o was the most potent compound from the synthesized series, with an anti-HIV-1 EC₅₀ value of 6.0 μM. However, this series of compounds showed a preference for HIV-2 inhibitory activity, in which Id-3o revealed an EC₅₀ value of 2.5 μM (anti-HIV-2 potency), an improvement over PF74. Interestingly, F-Id-3o did bind HIV-1 CA monomers and hexamers with comparable affinity, unlike PF74, consequently showing antiviral activity in the early and late stages of the HIV-1 lifecycle. Molecular

SUBMITTER: Zhang X 

PROVIDER: S-EPMC10357934 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature