Open AccessPrevention and treatment of SHIVAD8 infection in rhesus macaques by a potent d -peptide HIV entry inhibitor
Author(s) -
Yoshiaki Nishimura,
James N. Francis,
Olivia K. Donau,
Eric Jesteadt,
Reza Sadjadpour,
Amanda R. Smith,
Michael S. Seaman,
Brett D. Welch,
Malcolm A. Martin,
Michael S. Kay
Publication year - 2020
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2009700117
Subject(s) - rhesus macaque , macaque , potency , in vivo , peptide , human immunodeficiency virus (hiv) , clinical trial , pharmacology , nonhuman primate , virology , immunology , medicine , in vitro , biology , bioinformatics , biochemistry , neuroscience , microbiology and biotechnology , evolutionary biology
Cholesterol-PIE12-trimer (CPT31) is a potent d-peptide HIV entry inhibitor that targets the highly conserved gp41 N-peptide pocket region. CPT31 exhibited strong inhibitory breadth against diverse panels of primary virus isolates. In a simian-HIV chimeric virus AD8 (SHIVAD8) macaque model, CPT31 prevented infection from a single high-dose rectal challenge. In chronically infected animals, CPT31 monotherapy rapidly reduced viral load by ∼2 logs before rebound occurred due to the emergence of drug resistance. In chronically infected animals with viremia initially controlled by combination antiretroviral therapy (cART), CPT31 monotherapy prevented viral rebound after discontinuation of cART. These data establish CPT31 as a promising candidate for HIV prevention and treatment.
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