Li Shenwei, Kodama Eiichi N, Inoue Yuuki, Tani Hideki, Matsuura Yoshiharu, Zhang Jing, Tanaka Takashi, Hattori Toshio
Division of Emerging Infectious Diseases, Department of Internal Medicine, Tohoku University, Sendai, Japan.
Antivir Chem Chemother. 2010 Aug 11;20(6):239-48. doi: 10.3851/IMP1597.
A combination of pegylated interferon and ribavirin is the current standard therapy for hepatitis C virus (HCV) infection, but this combination provides relatively low efficacy, especially in some patients with HCV genotype 1 infection; therefore, the development of novel therapeutic agents is required for further improvement in the treatment of chronic HCV infection.
HCV pseudotype and subgenomic replicon assays were used in this study. The interaction of compounds with HCV receptors was examined using flow cytometry. Intracellular RNA levels were determined by semi-quantitative reverse transcriptase PCR.
Procyanidin B1 (PB1), a dimer of (-)-epicatechin and (+)-catechin, purified from Cinnamomi cortex, inhibits infection by vesicular stomatitis virus and HCV pseudotype virus in Huh-7 cells, with 50% effective concentrations of 29 and 15 microM, respectively. No inhibitory effects were observed in each component of PB1. We found that PB1 does not interfere with viral entry or receptor expression, but inhibits HCV RNA synthesis in a dose-dependent manner.
These results indicate that PB1 suppresses HCV RNA synthesis, possibly as a HCV RNA polymerase inhibitor. Our results might contribute towards the development of more effective inhibitors for HCV infection from natural plants.
聚乙二醇化干扰素和利巴韦林联合用药是目前丙型肝炎病毒(HCV)感染的标准治疗方法,但这种联合用药的疗效相对较低,尤其是在一些HCV 1型感染患者中;因此,需要开发新型治疗药物以进一步改善慢性HCV感染的治疗效果。
本研究采用HCV假型和亚基因组复制子分析方法。使用流式细胞术检测化合物与HCV受体的相互作用。通过半定量逆转录聚合酶链反应测定细胞内RNA水平。
从肉桂皮中纯化得到的原花青素B1(PB1),是(-)-表儿茶素和(+)-儿茶素的二聚体,在Huh-7细胞中可抑制水疱性口炎病毒和HCV假型病毒感染,50%有效浓度分别为29和15微摩尔。PB1的各组分均未观察到抑制作用。我们发现PB1不干扰病毒进入或受体表达,但以剂量依赖方式抑制HCV RNA合成。
这些结果表明,PB1可能作为HCV RNA聚合酶抑制剂抑制HCV RNA合成。我们的结果可能有助于从天然植物中开发出更有效的HCV感染抑制剂。