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

J Infect Dis. 2018 Jul 2;218(3):471-475. doi: 10.1093/infdis/jiy174.

Abstract

Background: 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.

Methods: The efficacy of a CD4mc in protecting bone marrow-liver-thymus (BLT) humanized mice from vaginal HIV-1 challenge was evaluated.

Results: 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.

Conclusion: The direct antiviral effects of a CD4mc prevent HIV-1 infection in a murine model of sexual transmission.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravaginal
  • Animals
  • Biomimetics*
  • Bone Marrow
  • CD4 Antigens / administration & dosage*
  • Disease Models, Animal
  • Female
  • HIV Fusion Inhibitors / administration & dosage*
  • HIV Infections / prevention & control*
  • HIV-1 / drug effects*
  • Liver
  • Mice, SCID
  • Thymus Gland
  • Treatment Outcome

Substances

  • CD4 Antigens
  • HIV Fusion Inhibitors