University of Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
Department of Biotechnology, Tocklai Tea Research Institute, TRA, Jorhat, Assam, India.
PLoS One. 2018 Nov 28;13(11):e0198226. doi: 10.1371/journal.pone.0198226. eCollection 2018.
The treatment of hepatitis C virus (HCV) infection by combination of direct acting antivirals (DAA), with different mode of action, has made substantial progress in the past few years. However, appearance of resistance and high cost of the therapy is still an obstacle in the achievement of the therapy, more specifically in developing countries. In this context, search for affordable antivirals with new mechanisms of action is still needed. Tea, after water, is the most popular drink worldwide. Polyphenols extracted from green tea have already shown anti-HCV activity as entry inhibitors. Here, three different theaflavins, theaflavin (TF1), theaflavin-3'-monogallate (TF2), and theaflavin-3-3'-digallate (TF3), which are major polyphenols from black tea, were tested against HCV in cell culture. The results showed that all theaflavins inhibit HCV infection in a dose-dependent manner in an early step of infection. Results obtained with HCV pseudotyped virions confirmed their activity on HCV entry and demonstrated their pan-genotypic action. No effect on HCV replication was observed by using HCV replicon. Investigation on the mechanism of action of black tea theaflavins showed that they act directly on the virus particle and are able to inhibit cell-to-cell spread. Combination study with inhibitors most widely used in anti-HCV treatment regimen demonstrated that TF3 exerts additive effect. In conclusion, theaflavins, that are present in high quantity in black tea, are new inhibitors of HCV entry and hold promise for developing in therapeutic arsenal for HCV infection.
直接作用抗病毒药物（DAA）联合治疗丙型肝炎病毒（HCV）感染在过去几年中取得了重大进展。然而，耐药性的出现和治疗的高成本仍然是实现治疗的障碍，特别是在发展中国家。在这种情况下，仍然需要寻找具有新作用机制的负担得起的抗病毒药物。茶是继水之后全球最受欢迎的饮品。从绿茶中提取的多酚已显示出作为进入抑制剂的抗 HCV 活性。在这里，三种不同的茶黄素，茶黄素（TF1）、茶黄素-3'-没食子酸酯（TF2）和茶黄素-3,3'-二没食子酸酯（TF3），它们是红茶中的主要多酚类物质，在细胞培养中被测试了对 HCV 的作用。结果表明，所有茶黄素都以剂量依赖的方式在感染的早期阶段抑制 HCV 的感染。使用 HCV 假型病毒粒子获得的结果证实了它们对 HCV 进入的活性，并证明了它们的泛基因型作用。用 HCV 复制子观察不到对 HCV 复制的影响。对红茶茶黄素作用机制的研究表明，它们直接作用于病毒颗粒，能够抑制细胞间传播。与抗 HCV 治疗方案中最广泛使用的抑制剂联合研究表明，TF3 具有相加作用。总之，茶黄素在红茶中含量很高，是 HCV 进入的新抑制剂，为 HCV 感染的治疗武器库的发展带来了希望。
