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

Novel inhibitors of human immunodeficiency virus type 2 infectivity

Lauren B Beach  1   2 , Jonathan M Rawson  1   2 , Baek Kim  3 , Steven E Patterson  4   2 , Louis M Mansky  4   1   2   5   6
Affiliations

Novel inhibitors of human immunodeficiency virus type 2 infectivity

Lauren B Beach et al. J Gen Virol. 2014 Dec.

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.

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Figures

Fig. 1.
Fig. 1.
Drugs investigated for activity against HIV-2. Drug structures are indicated.
Fig. 2.
Fig. 2.
Time-of-addition drug assay. Magi cells were seeded into 96-well plates and were then infected with VSV-G pseudotyped HIV-2 vector virus. At 0, 1, 2, 3, 4, 6, 8 and 24 h post-infection, cells were treated with no drug (DMSO only) or with the IC100 values of clofarabine (Clo), zidovudine (AZT), tenofovir (TFV), resveratrol (Res), raltegravir (Ral), 5-azacytidine (5AZC), or gemcitabine (Gem). Infections were performed in triplicate, background infectivity at the 0 h time point was subtracted, and infectivity for drug treatments was normalized to no drug (DMSO only) infectivity at the 24 h time point (which was 55 %). Values represent the means of three independent experiments, with each treatment at each time point treated in duplicate. Nevirapine was not analysed due to the lack of antiviral activity against HIV-2.
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