Approximately 142 million people worldwide are infected with hepatitis C virus (HCV). Although potent direct acting antivirals are available, high costs limit access to treatment. Chronic hepatitis C virus infection remains a major cause of orthotopic liver transplantation. Moreover, re-infection of the graft occurs regularly. Antivirals derived from natural sources might be an alternative and cost-effective option to complement therapy regimens for global control of hepatitis C virus infection.

We tested the antiviral properties of a mixture of different Chinese herbs/roots named Zhi Bai Di Huang Wan (ZBDHW) and its individual components on HCV. One of the ZBDHW components, Penta-O-Galloyl-Glucose (PGG), was further analyzed for its mode of action in vitro, its antiviral activity in primary human hepatocytes as well as for its bioavailability and hepatotoxicity in mice.

ZBDHW, its component Cortex Moutan and the compound PGG efficiently block entry of HCV of all major genotypes and also of the related flavivirus Zika virus. PGG does not disrupt HCV virion integrity and acts primarily during virus attachment. PGG shows an additive effect when combined with the well characterized HCV inhibitor Daclatasvir. Analysis of bioavailability in mice revealed plasma levels above tissue culture IC₅₀ after a single intraperitoneal injection.

In conclusion, PGG is a pangenotypic HCV entry inhibitor with high bioavailability. The low cost and wide availability of this compound make it a promising candidate for HCV combination therapies, and also emerging human pathogenic flaviviruses like ZIKV.

全世界大约有1.42亿人感染了丙型肝炎病毒（HCV）。尽管可以使用有效的直接作用抗病毒药，但高昂的费用限制了其获得治疗的机会。慢性丙型肝炎病毒感染仍然是原位肝移植的主要原因。而且，移植物的再感染经常发生。天然来源的抗病毒药物可能是替代疗法，并且具有成本效益，可以补充治疗方案，以全面控制丙型肝炎病毒感染。

我们测试了名为ZhiBadi Huang Wan（ZBDHW）的不同中草药/根混合物及其抗HCV的各个成分的抗病毒特性。ZBDHW成分之一Penta-O-Galloyl-葡萄糖（PGG）在体外的作用方式，在原代人肝细胞中的抗病毒活性以及在小鼠中的生物利用度和肝毒性被进一步分析。

ZBDHW，其组成成分Cortex Moutan和化合物PGG有效地阻止了所有主要基因型的HCV以及相关黄病毒Zika病毒的进入。PGG不会破坏HCV病毒粒子的完整性，并且主要在病毒附着过程中起作用。当与特征明确的HCV抑制剂Daclatasvir结合使用时，PGG显示出加和作用。小鼠的生物利用度分析显示，单次腹膜内注射后血浆血浆水平高于组织培养IC ₅₀。

总之，PGG是具有高生物利用度的全基因型HCV进入抑制剂。该化合物的低成本和广泛可用性使其成为HCV联合疗法以及新兴的人类致病性黄病毒（如ZIKV）的有希望的候选者。