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Prevention and treatment of SHIVAD8 infection in rhesus macaques by a potent d-peptide HIV entry inhibitor.
Nishimura, Yoshiaki; Francis, J Nicholas; Donau, Olivia K; Jesteadt, Eric; Sadjadpour, Reza; Smith, Amanda R; Seaman, Michael S; Welch, Brett D; Martin, Malcolm A; Kay, Michael S.
Afiliación
  • Nishimura Y; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.
  • Francis JN; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112.
  • Donau OK; Navigen, Inc., Salt Lake City, UT 84108.
  • Jesteadt E; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.
  • Sadjadpour R; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.
  • Smith AR; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.
  • Seaman MS; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112.
  • Welch BD; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215.
  • Martin MA; Navigen, Inc., Salt Lake City, UT 84108.
  • Kay MS; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892; malm@nih.gov kay@biochem.utah.edu.
Proc Natl Acad Sci U S A ; 117(36): 22436-22442, 2020 09 08.
Article en En | MEDLINE | ID: mdl-32820072
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / VIH / Virus de la Inmunodeficiencia de los Simios / Fármacos Anti-VIH / Internalización del Virus Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / VIH / Virus de la Inmunodeficiencia de los Simios / Fármacos Anti-VIH / Internalización del Virus Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos