Novel inhibitors of human immunodeficiency virus type 2 infectivity

被引：21

作者：

Beach, Lauren B. ^{[1
,2
]}

Rawson, Jonathan M. ^{[1
,2
]}

Kim, Baek ^{[3
]}

Patterson, Steven E. ^{[1
,4
]}

Mansky, Louis M. ^{[1
,2
,4
,5
,6
]}

机构：

[1] Univ Minnesota, Inst Mol Virol, Minneapolis, MN 55455 USA

[2] Univ Minnesota, Mol Cellular Dev Biol & Genet Grad Program, Minneapolis, MN 55455 USA

[3] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA

[4] Univ Minnesota, Ctr Drug Design, Minneapolis, MN 55455 USA

[5] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA

[6] Univ Minnesota, Dept Diagnost & Biol Sci, Sch Dent, Minneapolis, MN 55455 USA

来源：

JOURNAL OF GENERAL VIROLOGY | 2014年 / 95卷

关键词：

REVERSE-TRANSCRIPTASE INHIBITORS; ANTIRETROVIRAL DRUG-RESISTANCE; ANTI-HIV-1; ACTIVITY; SAMHD1; RESTRICTS; HIV-1; INFECTION; IN-VITRO; COMBINATION; THERAPY; INDIVIDUALS; MUTATIONS;

D O I：

10.1099/vir.0.069864-0

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：2778 / 2783

页数：6

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