دورية أكاديمية
Prevention and treatment of SHIVAD8 infection in rhesus macaques by a potent d-peptide HIV entry inhibitor.
| العنوان: | Prevention and treatment of SHIVAD8 infection in rhesus macaques by a potent d-peptide HIV entry inhibitor. |
|---|---|
| المؤلفون: | 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.; Navigen, Inc., Salt Lake City, UT 84108., Donau OK; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892., 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; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112., Seaman MS; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215., Welch BD; Navigen, Inc., Salt Lake City, UT 84108., Martin MA; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892; malm@nih.gov kay@biochem.utah.edu., Kay MS; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112; malm@nih.gov kay@biochem.utah.edu. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Sep 08; Vol. 117 (36), pp. 22436-22442. Date of Electronic Publication: 2020 Aug 20. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Anti-HIV Agents*/chemistry , Anti-HIV Agents*/pharmacology , Anti-HIV Agents*/therapeutic use , HIV*/drug effects , HIV*/genetics , HIV Infections*/drug therapy , HIV Infections*/prevention & control , HIV Infections*/virology , Simian Immunodeficiency Virus*/drug effects , Simian Immunodeficiency Virus*/genetics, Virus Internalization/*drug effects, Animals ; Drug Evaluation, Preclinical ; Female ; HIV Envelope Protein gp41/antagonists & inhibitors ; Macaca mulatta ; Male |
| مستخلص: | 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. Competing Interests: The authors declare no competing interest. (Copyright © 2020 the Author(s). Published by PNAS.) |
| التعليقات: | Erratum in: Proc Natl Acad Sci U S A. 2020 Sep 22;117(38):24003. (PMID: 32929023) |
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| معلومات مُعتمدة: | R56 AI076168 United States AI NIAID NIH HHS; R01 AI076168 United States AI NIAID NIH HHS; U44 AI095172 United States AI NIAID NIH HHS; R44 AI095172 United States AI NIAID NIH HHS; SB1 AI095172 United States AI NIAID NIH HHS; P50 AI150464 United States AI NIAID NIH HHS; R43 AI095172 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: HIV entry inhibitor; HIV prevention; HIV treatment; NHP HIV model; d-peptide |
| المشرفين على المادة: | 0 (Anti-HIV Agents) 0 (HIV Envelope Protein gp41) |
| تواريخ الأحداث: | Date Created: 20200822 Date Completed: 20201030 Latest Revision: 20240214 |
| رمز التحديث: | 20240214 |
| مُعرف محوري في PubMed: | PMC7486783 |
| DOI: | 10.1073/pnas.2009700117 |
| PMID: | 32820072 |
| قاعدة البيانات: | MEDLINE |
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