Cyclophilin inhibitors for the treatment of HCV infection.
Cyclophilin inhibitors for the treatment of HCV infection.
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发表时间：
2010-08
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通讯作者：
G. Fischer;P. Gallay;S. Hopkins
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作者：
G. Fischer;P. Gallay;S. Hopkins
亲环蛋白（Cyps）是肽基脯氨酸异构酶的三个家族之一。CypA是Cyp家族的典型成员，是人类细胞中表达的主要Cyp。最近的研究表明，CypA在支持hcv特异性RNA复制和蛋白表达方面发挥着重要作用。CypA与几种病毒表达的蛋白相互作用，包括非结构（NS）蛋白NS2、NS5A和NS5B，并可能调节从多肽加工到病毒组装的多种活性。将非免疫抑制性Cyp抑制剂引入临床试验，证实了Cyp抑制是开发治疗慢性HCV感染的新疗法的有效策略。这篇综述描述了亲环蛋白家族和亲环蛋白在支持HCV RNA复制和蛋白表达方面的潜在作用，以及一系列新的非免疫抑制性亲环蛋白抑制剂获得的初步临床结果，这些结果为这类新兴治疗剂的概念建立了临床证据。
Cyclophilins (Cyps) constitute one of the three families of peptidyl prolyl isomerase enzymes. CypA is the prototypical member of the Cyp family and is the predominant Cyp expressed in human cells. Recent studies indicate that CypA has an essential role in supporting HCV-specific RNA replication and protein expression. CypA interacts with several virally expressed proteins, including the non-structural (NS) proteins NS2, NS5A and NS5B, and may regulate diverse activities ranging from polypeptide processing to viral assembly. The introduction of non-immunosuppressive Cyp inhibitors into clinical trials confirms that Cyp inhibition is a valid strategy for developing novel therapeutics for the treatment of chronic HCV infection. This review describes the cyclophilin protein family and the potential roles played by cyclophilins in supporting HCV RNA replication and protein expression, as well as the initial clinical results obtained with a novel series of non-immunosuppressive cyclophilin inhibitors that established the clinical proof of concept for this emerging class of therapeutic agents.