Amy M Princiotto1, Vladimir D Vrbanac2, Bruno Melillo3, Jongwoo Park3, Andrew M Tager2, Amos B Smith3, Joseph Sodroski1,4,5, Navid Madani1,4,6. 1. Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts. 2. Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts. 3. Department of Chemistry, University of Pennsylvania, Philadelphia. 4. Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts. 5. Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. 6. Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts.
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.
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.
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