title: Novel inhibitors of human immunodeficiency virus type 2 infectivity.
abstract: Human immunodeficiency virus type 2 (HIV-2) infects about two million people worldwide. HIV-2 has fewer treatment options than HIV-1, yet may evolve drug resistance more quickly. We have analysed several novel drugs for anti-HIV-2 activity. It was observed that 5-azacytidine, clofarabine, gemcitabine and resveratrol have potent anti-HIV-2 activity. The EC50 values for 5-azacytidine, clofarabine and resveratrol were found to be significantly lower with HIV-2 than with HIV-1. A time-of-addition assay was used to analyse the ability of these drugs to interfere with HIV-2 replication. Reverse transcription was the likely target for antiretroviral activity. Taken together, several novel drugs have been discovered to have activity against HIV-2. Based upon their known activities, these drugs may elicit enhanced HIV-2 mutagenesis and therefore be useful for inducing HIV-2 lethal mutagenesis. In addition, the data are consistent with HIV-2 reverse transcriptase being more sensitive than HIV-1 reverse transcriptase to dNTP pool alterations.
authors.affiliation: Molecular, Cellular, Developmental Biology & Genetics Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA.|Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Beach
authors.affiliation: Molecular, Cellular, Developmental Biology & Genetics Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA.|Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Rawson
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Baek
authors.initials: B
authors.lastname: Kim
authors.affiliation: Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA.|Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Patterson
authors.affiliation: Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA.|Molecular, Cellular, Developmental Biology & Genetics Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA.|Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA.|Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA.|Department of Microbiology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Mansky
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D015498:HIV-2 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D016296:Mutagenesis / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors
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