Tannic Acid Inhibits Hepatitis C Virus Entry into Huh7.5 Cells.
Tannic Acid Inhibits Hepatitis C Virus Entry into Huh7.5 Cells.
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DOI：
10.1371/journal.pone.0131358
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hagedorn CH
中科院分区：
文献类型：
--
作者：
Liu S;Chen R;Hagedorn CH
丙型肝炎病毒（HCV）的慢性感染是全世界肝硬化和肝细胞癌的原因。尽管抗病毒治疗最近有了显着改善，但许多患者仍未得到治疗，有些患者未能通过治疗清除感染。病毒进入是引发和维持慢性丙型肝炎病毒感染的重要步骤。一个引人注目的例子是慢性丙型肝炎患者新移植肝脏的感染率接近 100%。HCV 进入抑制剂可以在预防新移植肝脏的 HCV 感染方面发挥关键作用。单宁酸是没食子酸和葡萄糖分子的聚合物，是一种植物源性多酚，可以保护某些植物免受昆虫和微生物感染。它已被证明具有多种生物效应，包括抗病毒活性，并用作食品和饮料中的调味剂。在这项研究中，我们证明单宁酸是低浓度 (IC50 5.8 μM) 的 HCV 进入 Huh7.5 细胞的有效抑制剂。它还可以阻止感染性 HCV 细胞培养物中的细胞间传播，但不会抑制感染后 HCV 的复制。此外，实验结果表明单宁酸抑制病毒进入的早期步骤，例如HCV在细胞表面的停靠。没食子酸（单宁酸的结构成分）没有表现出任何抗 HCV 活性，包括在浓度高达 25 μM 时抑制 HCV 进入或复制。单宁结构可能与 HCV 抑制作用有关。单宁酸广泛分布于植物和食品中，在细胞培养物中以低微摩尔浓度具有 HCV 抗病毒活性，可能为直接作用的 HCV 抗病毒药物提供相对便宜的佐剂，值得进一步研究。
Chronic infection with the hepatitis C virus (HCV) is a cause of cirrhosis and hepatocellular carcinoma worldwide. Although antiviral therapy has dramatically improved recently, a number of patients remain untreated and some do not clear infection with treatment. Viral entry is an essential step in initiating and maintaining chronic HCV infections. One dramatic example of this is the nearly 100% infection of newly transplanted livers in patients with chronic hepatitis C. HCV entry inhibitors could play a critical role in preventing HCV infection of newly transplanted livers. Tannic acid, a polymer of gallic acid and glucose molecules, is a plant-derived polyphenol that defends some plants from insects and microbial infections. It has been shown to have a variety of biological effects, including antiviral activity, and is used as a flavoring agent in foods and beverages. In this study, we demonstrate that tannic acid is a potent inhibitor of HCV entry into Huh7.5 cells at low concentrations (IC50 5.8 μM). It also blocks cell-to-cell spread in infectious HCV cell cultures, but does not inhibit HCV replication following infection. Moreover, experimental results indicate that tannic acid inhibits an early step of viral entry, such as the docking of HCV at the cell surface. Gallic acid, tannic acid’s structural component, did not show any anti-HCV activity including inhibition of HCV entry or replication at concentrations up to 25 μM. It is possible the tannin structure is related on the effect on HCV inhibition. Tannic acid, which is widely distributed in plants and foods, has HCV antiviral activity in cell culture at low micromolar concentrations, may provide a relative inexpensive adjuvant to direct-acting HCV antivirals and warrants future investigation.