A Small-Molecule CD4-Mimetic Compound Protects Bone Marrow-Liver-Thymus Humanized Mice From HIV-1 Infection.

Princiotto, Amy M; Vrbanac, Vladimir D; Melillo, Bruno; Park, Jongwoo; Tager, Andrew M; Smith, Amos B; Sodroski, Joseph; Madani, Navid · J Infect Dis · 2018

basic_science · Level V

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Abstract

Small-molecule CD4-mimetic compounds (CD4mc) inhibit human immunodeficiency virus (HIV-1) entry by blocking binding to the CD4 receptor and by premature triggering of the viral envelope glycoprotein (Env) spike. The efficacy of a CD4mc in protecting bone marrow-liver-thymus (BLT) humanized mice from vaginal HIV-1 challenge was evaluated. Intravaginal application of the CD4mc JP-III-48, either before or simultaneously with virus challenge, protected BLT humanized mice from HIV-1JR-CSF infection in a dose- dependent manner. The direct antiviral effects of a CD4mc prevent HIV-1 infection in a murine model of sexual transmission.

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