Epigallocatechin gallate inhibits the HIV reverse transcription step
Epigallocatechin gallate inhibits the HIV reverse transcription step
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DOI：
10.3851/imp1774
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发表时间：
2011-01-01
影响因子：
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通讯作者：
Kodama, Eiichi N.
中科院分区：
文献类型：
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作者：
Li, Shenwei;Hattori, Toshio;Kodama, Eiichi N.
背景资料：表没食子儿茶素没食子酸酯（Epigallocatechin gallate，EGCG）是绿色茶中含量最丰富的儿茶素，已报道其通过各种提出的机制在HIV-1整合到宿主DNA中之前抑制HIV-1复制;然而，EGCG的具体主要靶点仍不清楚。在这项研究中，我们研究了一些这些提出的详细机制（S）使用基于细胞的model.Methods：多核激活半乳糖苷酶指示剂测定用于所有实验，包括检查的时间添加和与核苷逆转录酶抑制剂，3 '-叠氮基-3'-脱氧胸苷（AZT）的协同作用。实验表明，EGCG抑制了HeLa-CD 4-LTR-β-gal细胞中的HIV-1（IIIB）和HIV-2（EHO）感染，其50%有效浓度分别为1.6和2.0 μ M。使用添加时间测定法产生的EGCG的抑制特性与非核苷逆转录酶抑制剂（NNRTI）MKC-442的抑制特性相同。此外，协同抑制中观察到的EGCG与AZT.Conclusions：根据我们的研究结果，EGCG似乎主要作为一种变构逆转录酶抑制剂的机制不同，目前批准的NNRTI，直接与NNRTI结合口袋。因此，表没食子儿茶素没食子酸酯是一个很好的候选人，作为一个额外的或支持性的抗艾滋病毒剂来自天然植物。
Background: Epigallocatechin gallate (EGCG), the most abundant catechin in green tea, has been reported to inhibit HIV-1 replication prior to its integration into host DNA via various proposed mechanisms; however, the specific main target(s) of EGCG remain unclear. In this study, we investigated a number of these proposed detailed mechanism(s) using a cell-based model.Methods: Multinuclear activation of galactosidase indicator assays were used for all experiments, including examination of the time of addition and the synergisms with a nucleoside reverse transcriptase inhibitor, 3'-azido-3'-deoxythymidine (AZT).Results: The experiments revealed that EGCG suppressed both HIV-1(IIIB) and HIV-2(EHO) infection in HeLa-CD4-LTR-beta-gal cells, with relatively low 50% effective concentrations of 1.6 and 2.0 mu M, respectively. The inhibitory profile of EGCG generated using a time-of-addition assay was identical to that of a non-nucleoside reverse transcriptase inhibitor (NNRTI), MKC-442. Furthermore, synergistic inhibition was observed in EGCG with AZT.Conclusions: Based on our findings, EGCG appears to act mainly as an allosteric reverse transcriptase inhibitor with mechanisms different from those of currently approved NNRTIs that directly interact with the NNRTI binding pocket. Thus, EGCG is a good candidate for use as an additional or supportive anti-HIV agent derived from natural plants.