A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes.
A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes.
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五味子衍生化合物五味子二酸抑制泛丙型肝炎病毒基因型进入人肝细胞
DOI：
10.1038/srep27268
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发表时间：
2016-06-02
影响因子：
4.6
通讯作者：
Qi ZT
中科院分区：
文献类型：
--
作者：
Qian XJ;Zhang XL;Zhao P;Jin YS;Chen HS;Xu QQ;Ren H;Zhu SY;Tang HL;Zhu YZ;Qi ZT
尽管最近丙型肝炎病毒(HCV)抑制剂的开发取得了进展，但成本效益高的抗病毒药物，特别是在接受肝移植的患者中，仍有待研究。五味子是中国几千年来用来治疗包括肝炎在内的一系列肝病的传统中草药。为了分离五味子抗丙型肝炎病毒的活性成分，我们筛选了五味子提取物文库，并鉴定了一种新的丙型肝炎病毒进入抑制剂--五味子三萜类化合物。我们的研究结果表明，SZA有效地抑制了PAN-丙型肝炎病毒进入肝癌细胞和原代人肝细胞，而不干扰病毒在细胞表面的结合或内化。然而，SZA的存在阻碍了病毒粒子与细胞的融合过程，并增加了宿主膜的流动性。我们还发现，SZA抑制了丙型肝炎病毒向邻近细胞的传播，并且SZA与干扰素或替拉维韦联合使用，对丙型肝炎病毒产生了相加的协同作用。此外，SZA还可减少体内丙型肝炎病毒感染的建立。SZA的靶点不同于传统的直接作用抗病毒药物，因此，SZA是一种潜在的治疗化合物，可用于开发有效的丙型肝炎病毒进入抑制剂，特别是对于需要预防肝移植过程中丙型肝炎病毒再感染的患者。
Despite recent progress in the development of hepatitis C virus (HCV) inhibitors, cost-effective antiviral drugs, especially among the patients receiving liver transplantations, are still awaited. Schisandra is a traditional medicinal herb used to treat a range of liver disorders including hepatitis for thousands of years in China. To isolate the bioactive compounds of schisandra for the treatment of HCV infection, we screened a schisandra-extracts library and identified a tetracyclic triterpenoid, schizandronic acid (SZA), as a novel HCV entry inhibitor. Our findings suggested that SZA potently inhibited pan-HCV genotype entry into hepatoma cells and primary human hepatocytes without interfering virus binding on cell surface or internalization. However, virion-cell fusion process was impaired in the presence of SZA, along with the increased host membrane fluidity. We also found that SZA inhibited the spread of HCV to the neighboring cells, and combinations of SZA with interferon or telaprevir resulted in additive synergistic effect against HCV. Additionally, SZA diminished the establishment of HCV infectionin vivo. The SZA target is different from conventional direct-acting antiviral agents, therefore, SZA is a potential therapeutic compound for the development of effective HCV entry inhibitors, especially for patients who need to prevent HCV reinfection during the course of liver transplantations.