丙型肝炎病毒入胞抑制剂的研究进展

Research on Hepatitis C Virus Entry Inhibitor

丙肝感染是全球性的公共卫生问题之一,目前尚无预防丙肝病毒感染的疫苗,联合应用靶向丙肝不同复制阶段的药物,即所谓的"鸡尾酒"疗法可能会有更好的疗效。丙肝病毒进入宿主细胞的过程是药物干预的重要环节,这个过程是由丙肝病毒的包膜蛋白与宿主因子作用介导的,其中病毒的包膜蛋白包括E1、E2,宿主因子包括硫酸乙酰肝素(Heparan sulfate,HS)、膜蛋白CD81、B族I型清道夫受体(Scavenger receptor class B type I,SR-BI)、两种紧密连接蛋白Occludin(OCLD)和Claudin(CLDN)、低密度脂蛋白受体(Low densitity lipoprotein receptor,LDLR)、树突细胞特异性细胞间黏附分子-3-结合非整合素分子(Dendritic cell-specific ICAM-3-grab-bing nonintegrin,DCSIGN)、肝/淋巴细胞特异性细胞间粘附分子-3-结合整合素分子(Liver/lymph node specific ICAM-3-grabbing integrin,L-SIGN)和转铁蛋白1受体(Transferrin receptor 1,TfR1)等。病毒的包膜蛋白和这些宿主因子都可以作为靶向丙肝入胞抑制剂的作用靶点,许多研究表明丙肝入胞抑制剂作为一种新颖和有发展前景的化合物与作用于复制阶段药物联合应用能够更有效的治疗丙肝。本文综述了自20世纪90年代以来发现的靶点和靶向丙肝病毒进入宿主细胞的化合物。

Hepatitis C virus （HCV） infection is a global public health issue, although no vaccine exists for the prevention of HCV infection. The so-called ＂cocktail＂ therapy, which uses a combination of drugs that target multiple steps in the HCV infection cycle, could achieve better curative effects. The process of HCV entering into host cells is an important step in drug interventions, in which the HCV envelope proteins E1 and E2, host cell factors including heparan sulfate （HS）, CD81, scavenger receptor class B type I （SR-BI）, occludin （OCLD）, claudin （CLDN）, low density lipoprotein receptor （LDLR）, dendritic cell-specific ICAM-3-grabbing nonintegrin （DC-SIGN）, liver/lymph node specific ICAM-3-grabbing integrin （L-SIGN）, transferrin receptor 1 （TfR1）, amongst others, play an important role. Both virus and host factors can be used as targets for HCV entry inhibitors. Many studies have shown that these novel and promising compounds combined with other drugs can be effective in the treatment of HCV. This paper reviews the targets and inhibitors of HCV entering host cells that have been established since the 1990s.