CD4-mimetic sulfopeptide conjugates display sub-nanomolar anti-HIV-1 activity and protect macaques against a SHIV162P3 vaginal challenge.

ABSTRACT: The CD4 and the cryptic coreceptor binding sites of the HIV-1 envelope glycoprotein are key to viral attachment and entry. We developed new molecules comprising a CD4 mimetic peptide linked to anionic compounds (mCD4.1-HS₁₂ and mCD4.1-PS1), that block the CD4-gp120 interaction and simultaneously induce the exposure of the cryptic coreceptor binding site, rendering it accessible to HS₁₂- or PS1- mediated inhibition. Using a cynomolgus macaque model of vaginal challenge with SHIV162P3, we report that mCD4.1-PS1, formulated into a hydroxyethyl-cellulose gel provides 83% protection (5/6 animals). We next engineered the mCD4 moiety of the compound, giving rise to mCD4.2 and mCD4.3 that, when conjugated to PS1, inhibited cell-free and cell-associated HIV-1 with particularly

SUBMITTER: Arien KK 

PROVIDER: S-EPMC5056392 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature