Dezecapavir

Dezecapavir (VH-499) is a HIV-1 capsid protein inhibitor. Dezecapavir exhibits picomolar-level antiviral activity against a variety of HIV-1 laboratory strains and clinical isolates in vitro. Dezecapavir inhibits the early and late stages of the HIV-1 life cycle, blocking nuclear import, reverse transcript production, virion assembly, maturation, and post-nuclear import/pre-integration replication processes. Dezecapavir can be used in studies related to HIV-1 infection ^{[1] [2]}.

In Vitro, Dezecapavir (0-4 days) inhibits the replication of HIV-1 NLRepRluc-WT in MT-2 cells, with a mean EC50 of 0.023 nM and extremely low cytotoxicity (CC50 >20 μM)^[2]. Dezecapavir inhibits the replication of multiple HIV-1 laboratory strains in A3R5-GFP/Luc cells, with a mean EC50 of 0.042 nM^[2]. Dezecapavir (0-72 h) potently inhibits the early (EC50 0.036 nM) and late (EC50 0.50 nM) stages of HIV-1 replication in a two-cell assay system, and reduces viral p24 release from HEK 293T cells with an IC₅₀ of 1.2 nM^[2]. Dezecapavir (50 nM; 96 h post-infection) blocks HIV-1 replication in MT-2 cells after reverse transcription is completed but before proviral integration, as evidenced by its time-of-addition inhibition curve^[2].

References:
[1]. Thakkar N, et al. Clinical Pharmacokinetics and Safety of Orally Administered VH4011499, a New HIV-1 Capsid Inhibitor, in Adults Without HIV. Infect Dis Ther. 2025;14(5):1011-1025.
[2]. Wang C, et al. Preclinical virology profiles of the HIV-1 capsid inhibitors VH4004280 and VH4011499. Antimicrob Agents Chemother. 2025;69(10):e0030925.