ArticleRSC medicinal chemistry2025
Design of a highly potent bifunctional HIV-1 entry inhibitor targeting both gp120 and gp41.
Article in RSC medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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9 authors.
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Abstract
Previous studies have demonstrated the essential role of the envelope glycoprotein (Env) gp120 and gp41 N-terminal heptad repeat (NHR) region in human immunodeficiency virus type 1 (HIV-1) life cycle steps. Based on the multitarget-directed ligand (MTDL) design strategy, we herein report a series of bifunctional entry inhibitors consisting of an aroyl indoleoxoacetyl piperazine-based attachment inhibitor, IAC, and a gp41 NHR-targeting peptide fusion inhibitor SP22. We found that one of these chimeras, named ISP, showed potent inhibitory potency against HIV-1, about 180- and 54-fold over that of its parent inhibitors, IAC and SP22, respectively. Our work provides a potent peptide-based bifunctional HIV-1 entry inhibitor and offers new insights into the design of therapies against infection of other enveloped viruses.
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