Modulation of host metabolism as a target of new antivirals.
Modulation of host metabolism as a target of new antivirals.
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DOI：
10.1016/j.addr.2007.03.021
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发表时间：
2007-10-10
影响因子：
16.1
通讯作者：
Kato N
中科院分区：
文献类型：
--
作者：
Ikeda M;Kato N
慢性丙型肝炎（CH-C）的治疗始于20世纪90年代初的干扰素（IFN）单药治疗，该治疗被认为在约10%的病例中有效。目前的标准疗法聚乙二醇干扰素与利巴韦林实现了持续的病毒学反应，约50%的患者。然而，大约一半的CH-C患者仍然有致命的肝硬化和肝细胞癌的风险。丙型肝炎病毒（HCV）研究中的另一个重要事件是细胞培养系统的发展。亚基因组复制子系统使得能够在肝癌细胞中稳健地复制HCV RNA。最近，使用基因型2a株JFH 1已经实现了HCV的完整生命周期。这些标志提供了许多关于HCV复制机制的信息，包括复制所需的宿主分子的信息。针对HCV蛋白的抗HCV试剂已经开发出来，其中一些已经进入临床试验阶段。然而，RNA依赖性RNA聚合酶经常导致HCV基因组突变，从而导致耐药HCV突变体的出现。已经使用HCV细胞培养系统发现了一些对HCV RNA复制至关重要的细胞蛋白。这些宿主分子也是抗病毒药物的候选靶标。本文就靶向宿主代谢的抗HCV试剂的研究进展作一综述。
The therapy for chronic hepatitis C (CH–C) started with interferon (IFN) monotherapy in the early 1990s and this therapy was considered effective in about 10% of cases. The present standard therapy of pegylated IFN with ribavirin achieves a sustained virologic response in about 50% of patients. However, about half of the CH–C patients are still at risk of fatal liver cirrhosis and hepatocellular carcinoma. The other significant event in hepatitis C virus (HCV) research has been the development of a cell culture system. The subgenomic replicon system enables robust HCV RNA replication in hepatoma cells. And recently, the complete life cycle of HCV has been achieved using a genotype 2a strain, JFH1. These hallmarks have provided much information about the mechanisms of HCV replication, including information on the host molecules required for the replication. Anti-HCV reagents targeting HCV proteins have been developed, and some of them are now in clinical trials. However, the RNA-dependent RNA polymerase frequently causes mutations in the HCV genome, which lead to the emergence of drug-resistant HCV mutants. Some of the cellular proteins essential for HCV RNA replication have already been discovered using the HCV cell culture system. These host molecules are also candidate targets for antivirals. Here, we describe the recent progress regarding the anti-HCV reagents targeting host metabolism.
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