丙型肝炎病毒靶向药物及抗病毒药物筛选

丙型肝炎由丙型肝炎病毒(hepatitis C virus,HCV)感染所致,约80%感染者可发展成慢性肝炎,甚至肝硬化和肝癌。目前,临床主要应用干扰素结合利巴韦林联合疗法治疗丙型肝炎,但治疗后病毒有效应答率不高,并伴有明显的副作用产生,迫切需要研发靶向药物。随着HCV体外细胞培养技术获得的突破性进展以及在此基础上各种药物筛选方法的建立,利用现有的筛选模型筛选靶向药物成为抗病毒药物研发的重要途径。近年来,将GFP、hRLuc等报告基因插入HCV基因组中改造成具有明显标记的高通量药物筛选体系,已初步筛选出一些有效的HCV靶向药物,就现有抗丙型肝炎病毒靶向药物及抗病毒药物筛选方法进行综述。

Hepatitis C Virus Targeting Drug and Drug Screening System

Hepatitis C virus (HCV) is the primary pathogen of hepatitis C and approximately 80% of infected persons translate chronic hepatitis, even cirrhosis and hepatocellular carcinoma. At present, the clinical therapy is a combination therapy of pegylated interferon-α (IFN) and ribavirin. However, the sustained virologic response (SVR) rate after treatment is not satisfied. In addition, IFN/ribavirin treatment is associated with obvious side effects. Therefore, it is urgent to develop the virus specific targeting drugs. With the breakthrough of HCV cell culture (HCVcc) technique, various anti-HCV drug screening methods were developed and applied to screen targeted drugs. Furthermore, the reporter genes of green fluorescent protein (GFP) and humanized renilla luciferase (hRLuc) were inserted into recombinant plasmid to establish the high-throughput drug screening systems, and a number of effective HCV targeted drugs have been screened out. The existed HCV targeting drug as well as the related drug screening system was summarized.