丙型肝炎病毒入胞抑制剂的研究进展

发布时间：2018-10-31 17:21

【摘要】：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。
[Abstract]:Hepatitis C infection is one of the global public health problems. There is no vaccine to prevent hepatitis C virus infection. The process of HCV entering host cells is an important part of drug intervention. This process is mediated by the interaction between HCV envelope protein and host factor. Host factors include heparin sulfate (Heparan sulfate,HS), membrane protein CD81,B type I scavenger receptor (Scavenger receptor class B type Ignor SR-BI, two tight junction proteins Occludin (OCLD) and Claudin (CLDN), Low density lipoprotein receptor (Low densitity lipoprotein receptor,LDLR), dendritic cell-specific intercellular adhesion molecule-3 binding non integrin molecule (Dendritic cell-specific ICAM-3-grab-bing nonintegrin,DCSIGN), Liver / lymphocyte specific intercellular adhesion molecule-3 binding integrin molecule (Liver/lymph node specific ICAM-3-grabbing integrin,L-SIGN) and transferrin 1 receptor (Transferrin receptor 1 TfR1). Both the envelope protein of the virus and these host factors can be used as targets for the targeting of hepatitis C inhibitors. Many studies have shown that hepatitis C inhibitors as a novel and promising compound combined with drugs acting on replication stage can be more effective in the treatment of hepatitis C. In this paper, the targets and compounds targeting HCV entering host cells have been reviewed since 1990's.
【作者单位】：南方医科大学;广东药学院基础学院药用生物活性物质研究所;广东省生物活性药物研究重点实验室;
【基金】：国家科技部新药创制重大专项项目(2013ZX09103003-003)资助
【分类号】：R373.21

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