Journal article
Antiviral Breadth and Combination Potential of Peptide Triazole HIV-1 Entry Inhibitors
Antimicrobial agents and chemotherapy, v 56(2), pp 1073-1080
Feb 2012
PMID: 22083481
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The first stage of human immunodeficiency virus type 1 (HIV-1) infection involves the fusion of viral and host cellular membranes mediated by viral envelope glycoprotein gp120. Inhibitors that specifically target gp120 are gaining increased attention as therapeutics or preventatives to prevent the spread of HIV-1. One promising new group of inhibitors is the peptide triazoles, which bind to gp120 and simultaneously block its interaction with both CD4 and the coreceptor. In this study, we assessed the most potent peptide triazole, HNG-156, for inhibitory breadth, cytotoxicity, and efficacy, both alone and in combination with other antiviral compounds, against HIV-1. HNG-156 inhibited a panel of 16 subtype B and C isolates of HIV-1 in a single-round infection assay. Inhibition of cell infection by replication-competent clinical isolates of HIV-1 was also observed with HNG-156. We found that HNG-156 had a greater than predicted effect when combined with several other entry inhibitors or the reverse transcriptase inhibitor tenofovir. Overall, we find that HNG-156 is noncytotoxic, has a broad inhibition profile, and provides a positive combination with several inhibitors of the HIV-1 life cycle. These results support the pursuit of efficacy and toxicity analyses in more advanced cell and animal models to develop peptide triazole family inhibitors of HIV-1 into antagonists of HIV-1 infection.
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Details
- Title
- Antiviral Breadth and Combination Potential of Peptide Triazole HIV-1 Entry Inhibitors
- Creators
- Karyn McFadden - Department of Biochemistry, Drexel University College of Medicine, Philadelphia, PennsylvaniaPatricia Fletcher - St. Georges University London, London, United KingdomFiorella Rossi - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PennsylvaniaKantharaju - Department of Biochemistry, Drexel University College of Medicine, Philadelphia, PennsylvaniaMuddagowda Umashankara - Department of Biochemistry, Drexel University College of Medicine, Philadelphia, PennsylvaniaVanessa Pirrone - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PennsylvaniaSrivats Rajagopal - Department of Biochemistry, Drexel University College of Medicine, Philadelphia, PennsylvaniaHosahudya Gopi - Indian Institute of Science Education and Research, Pune, IndiaFred C Krebs - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PennsylvaniaJulio Martin-Garcia - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PennsylvaniaRobin J Shattock - St. Georges University London, London, United KingdomIrwin Chaiken - Department of Biochemistry, Drexel University College of Medicine, Philadelphia, Pennsylvania
- Publication Details
- Antimicrobial agents and chemotherapy, v 56(2), pp 1073-1080
- Publisher
- American Society for Microbiology; 1752 N St., N.W., Washington, DC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Microbiology and Immunology; Computer Science
- Web of Science ID
- WOS:000299658900063
- Scopus ID
- 2-s2.0-84856076358
- Other Identifier
- 991014878169104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Microbiology
- Pharmacology & Pharmacy