Suppression of hepatitis C virus by the flavonoid quercetin is mediated by inhibition of NS3 protease activity
Suppression of hepatitis C virus by the flavonoid quercetin is mediated by inhibition of NS3 protease activity
复制标题
DOI：
10.1111/j.1365-2893.2011.01507.x
复制
发表时间：
2012-02-01
影响因子：
2.5
通讯作者：
Zemel, R.
中科院分区：
文献类型：
--
作者：
Bachmetov, L.;Gal-Tanamy, M.;Zemel, R.
.植物化学物质具有抗病毒活性，可能在丙型肝炎病毒（HCV）感染中发挥潜在的治疗作用。在这项工作中，我们的目的是从传统的印度药用植物中分离NS 3抑制剂，在我们早期的研究中发现，抑制HCV NS 3蛋白酶活性，并评估其抑制HCV复制的潜力。用酸藤子植物提取物获得了NS 3催化活性的有效抑制作用。槲皮素是一种普遍存在的植物黄酮类化合物，被鉴定为分级提取物中的活性物质。在体外催化测定中发现其以特定的剂量依赖性方式抑制NS 3活性。槲皮素抑制丙型肝炎病毒RNA复制的分析，在亚基因组丙型肝炎病毒RNA复制子系统。它还抑制HCV感染性细胞培养系统（HCV-ET）中HCV感染性病毒的产生，通过焦点形成单位减少测定和HCV RNA实时PCR分析。槲皮素的抑制作用也获得了当使用模型系统，其中NS 3工程底物被引入到NS 3表达细胞，提供证据表明，在体内的抑制作用可以直接到NS 3和不涉及其他HCV蛋白。我们的工作表明槲皮素对HCV NS 3蛋白酶具有直接抑制作用。这些结果表明槲皮素作为一种天然无毒抗HCV药物的潜力，通过抑制HCV复制所必需的NS 3和热休克蛋白来减少病毒的产生。
. Phytochemicals exert antiviral activity and may play a potential therapeutic role in hepatitis C virus (HCV) infection. In this work, we aimed to isolate NS3 inhibitors from traditional Indian medicinal plants that were found, in our earlier study, to inhibit HCV NS3 protease activity and to evaluate their potential to inhibit HCV replication. A potent inhibitory effect of NS3 catalytic activity was obtained with Embelia ribes plant extracts. Quercetin, a ubiquitous plant flavonoid, was identified as the active substance in the fractioned extract. It was found to inhibit NS3 activity in a specific dose-dependent manner in an in vitro catalysis assay. Quercetin inhibited HCV RNA replication as analysed in the subgenomic HCV RNA replicon system. It also inhibited HCV infectious virus production in the HCV infectious cell culture system (HCVcc), as analysed by the focus-forming unit reduction assay and HCV RNA real-time PCR. The inhibitory effect of quercetin was also obtained when using a model system in which NS3 engineered substrates were introduced in NS3-expressing cells, providing evidence that inhibition in vivo could be directed to the NS3 and do not involve other HCV proteins. Our work demonstrates that quercetin has a direct inhibitory effect on the HCV NS3 protease. These results point to the potential of quercetin as a natural nontoxic anti-HCV agent reducing viral production by inhibiting both NS3 and heat shock proteins essential for HCV replication.