Evaluation of the anti-hepatitis C virus effects of cyclophilin inhibitors, cyclosporin A, and NIM811
Evaluation of the anti-hepatitis C virus effects of cyclophilin inhibitors, cyclosporin A, and NIM811
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DOI：
10.1016/j.bbrc.2006.03.059
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发表时间：
2006-05-12
影响因子：
3.1
通讯作者：
Shimotohno, K
中科院分区：
文献类型：
--
作者：
Goto, K;Watashi, K;Shimotohno, K
丙型肝炎病毒（HCV）是肝细胞癌的主要病原体。我们最近发现免疫抑制剂环孢菌素A（CsA）及其类似物缺乏免疫抑制功能，NIM 811，强烈抑制HCV在细胞培养中的复制。细胞复制辅因子亲环蛋白（CyP）B的抑制对其抗HCV作用至关重要。在这里，我们通过分析HCV复制子系统来探索CyP抑制剂用于HCV治疗的潜在用途。用CsA和NIM 811治疗7天可使HCV RNA水平降低2 - 3个log，治疗3周可使HCV RNA降低至无法检测的水平。在较低浓度下，NIM811的抗HCV活性高于CsA。这两种CyP抑制剂与IFN α联合使用时可进一步快速降低HCV RNA水平，而不会改变IFN α信号转导途径。总之，CyP抑制剂可以提供用于抗HCV治疗的新策略。All rights reserved.
Hepatitis C virus (HCV) is a major causative agent of hepatocellular carcinoma. We recently discovered that the immunosuppressant cyclosporin A (CsA) and its analogue lacking immunosuppressive function, NIM811, strongly suppress the replication of HCV in cell culture. Inhibition of a cellular replication cofactor, cyclophilin (CyP) B, is critical for its anti-HCV effects. Here, we explored the potential use of CyP inhibitors for HCV treatment by analyzing the HCV replicon system. Treatment with CsA and NIM811 for 7 days reduced HCV RNA levels by 2-3 logs, and treatment for 3 weeks reduced HCV RNA to undetectable levels. NIM811 exerted higher anti-HCV activity than CsA at lower concentrations. Both CyP inhibitors rapidly reduced HCV RNA levels even further in combination with IFN alpha without modifying the IFN alpha signal transduction pathway. In conclusion, CyP inhibitors may provide a novel strategy for anti-HCV treatment, (c) 2006 Elsevier Inc. All rights reserved.