Novel inhibitors of human immunodeficiency virus type 2 infectivity

J Gen Virol. 2014 Dec;95(Pt 12):2778-2783. doi: 10.1099/vir.0.069864-0. Epub 2014 Aug 7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Cell Line
  • HIV-2 / drug effects*
  • HIV-2 / genetics
  • HIV-2 / physiology
  • Humans
  • Mutagenesis / drug effects
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Reverse Transcriptase Inhibitors