期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 21, 期 22, 页码 7222-7228出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2013.08.023
关键词
Lethal mutagenesis; Error catastrophe; Resveratrol; KP-1212; 5,6-Dihydro-5-aza-2 '-deoxycytidine
资金
- NIH [R01 GM56615, R21 AI96937, F31DA030249, T32DA007097]
- Institute for Molecular Virology Training Program (NIH) [T32AI83196]
- MinnCResT Program (NIH) [T32DE007288]
- University of Minnesota Basic Sciences PhD Graduate Programs Council Fellowship
The nucleoside analog 5,6-dihydro-5-aza-2'-deoxycytidine (KP-1212) has been investigated as a first-in-class lethal mutagen of human immunodeficiency virus type-1 (HIV-1). Since a prodrug monotherapy did not reduce viral loads in Phase II clinical trials, we tested if ribonucleotide reductase inhibitors (RNRIs) combined with KP-1212 would improve antiviral activity. KP-1212 potentiated the activity of gemcitabine and resveratrol and simultaneously increased the viral mutant frequency. G-to-C mutations predominated with the KP-1212-resveratrol combination. These observations represent the first demonstration of a mild anti-HIV-1 mutagen potentiating the antiretroviral activity of RNRIs and encourage the clinical translation of enhanced viral mutagenesis in treating HIV-1 infection. (C) 2013 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据