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drug resistance

  • Therapeutic Efficacy and Resistance Selection of a Lipopeptide Fusion Inhibitor in Simian Immunodeficiency Virus-Infected Rhesus Macaques
    Vaccines and Antiviral Agents
    Therapeutic Efficacy and Resistance Selection of a Lipopeptide Fusion Inhibitor in Simian Immunodeficiency Virus-Infected Rhesus Macaques

    The anti-HIV peptide drug T20 (enfuvirtide) is the only membrane fusion inhibitor available for treatment of viral infection; however, it exhibits relatively weak antiviral activity, short half-life, and a low genetic barrier to inducing drug resistance. Design of lipopeptide-based fusion inhibitors with extremely potent and broad antiviral activities against divergent HIV-1, HIV-2, and SIV isolates have provided drug candidates for...

    Danwei Yu, Jing Xue, Huamian Wei, Zhe Cong, Ting Chen, Yuanmei Zhu, Huihui Chong, Qiang Wei, Chuan Qin, Yuxian He
  • Open Access
    Long-Acting Rilpivirine (RPV) Preexposure Prophylaxis Does Not Inhibit Vaginal Transmission of RPV-Resistant HIV-1 or Select for High-Frequency Drug Resistance in Humanized Mice
    Vaccines and Antiviral Agents
    Long-Acting Rilpivirine (RPV) Preexposure Prophylaxis Does Not Inhibit Vaginal Transmission of RPV-Resistant HIV-1 or Select for High-Frequency Drug Resistance in Humanized Mice

    The antiretroviral drug rilpivirine was developed into a long-acting formulation (RPV LA) to improve adherence for preexposure prophylaxis (PrEP) to prevent HIV-1 transmission. A concern is that RPV LA will not inhibit transmission of drug-resistant HIV-1 and may select for drug-resistant virus. In female humanized mice, we found that RPV LA inhibited vaginal transmission of WT or 3-fold RPV-resistant HIV-1 but not virus with 30-fold...

    Kevin Melody, Chandra N. Roy, Christopher Kline, Mackenzie L. Cottrell, Dwayne Evans, Kathleen Shutt, Pleuni S. Pennings, Brandon F. Keele, Moses Bility, Angela D. M. Kashuba, Zandrea Ambrose
  • Adaptive Mutations in Replicase Transmembrane Subunits Can Counteract Inhibition of Equine Arteritis Virus RNA Synthesis by Cyclophilin Inhibitors
    Vaccines and Antiviral Agents
    Adaptive Mutations in Replicase Transmembrane Subunits Can Counteract Inhibition of Equine Arteritis Virus RNA Synthesis by Cyclophilin Inhibitors

    Currently, no approved treatments are available to combat infections with nidoviruses, a group of positive-stranded RNA viruses, including important zoonotic and veterinary pathogens. Previously, the cyclophilin inhibitors cyclosporine (CsA) and alisporivir (ALV) were shown to inhibit the replication of diverse nidoviruses (both arteriviruses and coronaviruses), and they may thus represent a class of pan-nidovirus inhibitors. In this...

    Adriaan H. de Wilde, A. Linda Boomaars-van der Zanden, Anja W. M. de Jong, Montserrat Bárcena, Eric J. Snijder, Clara C. Posthuma
  • An E460D Substitution in the NS5 Protein of Tick-Borne Encephalitis Virus Confers Resistance to the Inhibitor Galidesivir (BCX4430) and Also Attenuates the Virus for Mice
    Vaccines and Antiviral Agents | Spotlight
    An E460D Substitution in the NS5 Protein of Tick-Borne Encephalitis Virus Confers Resistance to the Inhibitor Galidesivir (BCX4430) and Also Attenuates the Virus for Mice

    Tick-borne encephalitis virus (TBEV) is a pathogen that causes severe human neuroinfections in Europe and Asia and for which there is currently no specific therapy. We have previously found that galidesivir (BCX4430), a broad-spectrum RNA virus inhibitor, which is under clinical development for treatment of Ebola and yellow fever virus infections, has a strong antiviral effect against TBEV. For any antiviral drug, it is important to...

    Ludek Eyer, Antoine Nougairède, Marie Uhlířová, Jean-Sélim Driouich, Darina Zouharová, James J. Valdés, Jan Haviernik, Ernest A. Gould, Erik De Clercq, Xavier de Lamballerie, Daniel Ruzek
  • Open Access
    Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs
    Vaccines and Antiviral Agents
    Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs

    Although antiretroviral therapy (ART) is highly successful, drug-resistant variants can arise that blunt the efficacy of ART. New inhibitors that are broadly effective against known drug-resistant variants are needed, although such compounds might select for novel resistance mutations that affect the sensitivity of the virus to other compounds. Compound 13 selects for resistance mutations that differ from traditional NNRTI resistance...

    Paul L. Boyer, Kevin Melody, Steven J. Smith, Linda L. Dunn, Chris Kline, Douglas K. Fischer, Richa Dwivedi, Pat Clark, Stephen H. Hughes, Zandrea Ambrose
  • Virus-Cell Interactions
    Mutations in the Fusion Protein of Measles Virus That Confer Resistance to the Membrane Fusion Inhibitors Carbobenzoxy-d-Phe-l-Phe-Gly and 4-Nitro-2-Phenylacetyl Amino-Benzamide
    Michael N. Ha, Sébastien Delpeut, Ryan S. Noyce, Gary Sisson, Karen M. Black, Liang-Tzung Lin, Darius Bilimoria, Richard K. Plemper, Gilbert G. Privé, Christopher D. Richardson
  • Genetic Diversity and Evolution
    Tracking the Evolution of Multiple In Vitro Hepatitis C Virus Replicon Variants under Protease Inhibitor Selection Pressure by 454 Deep Sequencing
    Thierry Verbinnen, Herwig Van Marck, Ina Vandenbroucke, Leen Vijgen, Marijke Claes, Tse-I Lin, Kenneth Simmen, Johan Neyts, Gregory Fanning, Oliver Lenz
  • Vaccines and Antiviral Agents
    “Resistance” to PSC-RANTES Revisited: Two Mutations in Human Immunodeficiency Virus Type 1 HIV-1SF162 or Simian-Human Immunodeficiency Virus SHIVSF162-p3 Do Not Confer Resistance
    Rebecca Nedellec, Mia Coetzer, Michael M. Lederman, Robin E. Offord, Oliver Hartley, Donald E. Mosier
  • Pathogenesis and Immunity
    Role of Complex Carbohydrates in Human Immunodeficiency Virus Type 1 Infection and Resistance to Antibody Neutralization
    James M. Binley, Yih-En Andrew Ban, Emma T. Crooks, Dirk Eggink, Keiko Osawa, William R. Schief, Rogier W. Sanders
  • GENE THERAPY
    Development of Murine Leukemia Virus-Based Self-Activating Vectors That Efficiently Delete the Selectable Drug Resistance Gene during Reverse Transcription
    Krista A. Delviks, Vinay K. Pathak
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