Fischer Gunter, Gallay Philippe, Hopkins Sam
Max-Planck Research Unit for Enzymology and Protein Folding, Weinbergweg 22, Halle/Saale D-06120, Germany
Curr Opin Investig Drugs. 2010 Aug;11(8):911-8.
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.
亲环蛋白（Cyps）是肽基脯氨酰异构酶家族的三个成员之一。亲环蛋白A（CypA）是亲环蛋白家族的典型成员，也是人类细胞中表达的主要亲环蛋白。最近的研究表明，CypA在支持丙型肝炎病毒（HCV）特异性RNA复制和蛋白质表达方面起着至关重要的作用。CypA与几种病毒表达的蛋白质相互作用，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等多种活动。将非免疫抑制性亲环蛋白抑制剂引入临床试验证实，抑制亲环蛋白是开发治疗慢性HCV感染新疗法的有效策略。这篇综述描述了亲环蛋白家族以及亲环蛋白在支持HCV RNA复制和蛋白质表达中所起的潜在作用，以及一系列新型非免疫抑制性亲环蛋白抑制剂所获得的初步临床结果，这些结果为这类新兴治疗药物建立了临床概念验证。
