Fostemsavir analog BMS-818251 has enhanced viral neutralization potency and similar escape mutation profile.

ABSTRACT: BMS-818251, a fostemsavir analog, is a next-generation HIV-1 attachment inhibitor with enhanced potency and a similar resistance profile. By using ex vivo viral outgrowth assays with HIV+ donor samples, we demonstrate here that BMS-818251 exhibits superior viral suppression compared to temsavir, the active form of fostemsavir. To map potential resistance pathways, we employed deep mutational scanning and pseudotyped virus neutralization assays to identify escape mutations within the HIV-1 envelope glycoprotein (Env). These mutations were largely clustered around the BMS-818251 binding site, with key resistance mutations reducing drug-binding affinity. Several of the enriched mutations, such as S375I/N, M426L, and M475I, have been previously observed in fostemsavir-treated patients,

SUBMITTER: Lai Y-T 

PROVIDER: S-EPMC12486810 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature