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J Gen Virol. 2014 Dec;95(Pt 12):2778-83. doi: 10.1099/vir.0.069864-0. Epub 2014 Aug 7.

Novel inhibitors of human immunodeficiency virus type 2 infectivity.

Author information

1
Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA Molecular, Cellular, Developmental Biology & Genetics Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA.
2
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
3
Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA.
4
Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA Molecular, Cellular, Developmental Biology & Genetics Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA Department of Microbiology, University of Minnesota, Minneapolis, MN 55455, USA Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA mansky@umn.edu.

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.

PMID:
25103850
PMCID:
PMC4233633
DOI:
10.1099/vir.0.069864-0
[Indexed for MEDLINE]
Free PMC Article

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