Hydrolyzable tannins punicalin and geraniin block hepatitis C virus life cycle

Hydrolyzable tannins were reported to exert inhibitory effects on the infection and replication of several viruses such as HBV, HSV, HIV and leukemia virus. Here we found antiviral effects of two hydrolyzable tannins, punicalin and geraniin, on the HCV life cycle. Our results showed the two hydrolyzable tannins inhibit both attachment and penetration steps of HCV entry. We also verified they suppressed the infection of HCV pseudo-particles. Intriguingly, punicalin and geraniin were found to exert antiviral activities on HCV replicon system. Further study showed HCV NS3/4A serine protease activity was inhibited by the compounds at both the molecular level and the cellular level. Moreover, the two hydrolyzable tannins impeded infectious virion production into culture supernatants. Taken together, hydrolyzable tannins punicalin and geraniin block at least two stages of the HCV life cycle and may be promising lead compounds for the development of anti-HCV agents.

据报道，可水解单宁对多种病毒的感染和复制具有抑制作用，例如乙型肝炎病毒（HBV）、单纯疱疹病毒（HSV）、人类免疫缺陷病毒（HIV）和白血病病毒。本研究发现，两种可水解单宁—— punicalin 和 geraniin，对丙型肝炎病毒（HCV）的生命周期具有抗病毒作用。研究结果表明，这两种可水解单宁可抑制 HCV 进入过程中的附着和穿透步骤。此外，我们还证实了它们能够抑制 HCV 假病毒颗粒的感染。令人好奇的是，punicalin 和 geraniin 在 HCV 复制子系统中表现出抗病毒活性。进一步研究表明，这两种化合物在分子水平和细胞水平上均抑制了 HCV NS3/4A 硫酸酯蛋白酶的活性。此外，这两种可水解单宁还阻碍了感染性病毒颗粒在培养基上清中的产生。综上所述，可水解单宁 punicalin 和 geraniin 至少阻断 HCV 生命周期中的两个阶段，并可能成为开发抗 HCV 药剂的潜在先导化合物。