Novel inhibitors of human immunodeficiency virus type 2 infectivity

Lauren B. Beach, Jonathan M. Rawson, Baek Kim, Steven E. Patterson, Louis M. Mansky

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2778-2783
Number of pages6
JournalJournal of General Virology
Volume95
DOIs
StatePublished - Dec 1 2014

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