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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >The cyclophilin inhibitor debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus
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The cyclophilin inhibitor debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus

机译：亲环素抑制剂debio-025在合并感染丙型肝炎和人类免疫缺陷病毒的患者中显示出有效的抗丙型肝炎作用

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摘要

Debio-025 is an oral cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double-blind, placebo-controlled study. Mean hepatitis C viral load decreased significantly by 3.6 log(10) after a 14-day oral treatment with 1200 mg twice daily (P < 0.0001) with an effect against the 3 genotypes (1, 3, and 4) represented in the study. In addition, the absence of viral rebound during treatment indicates that Debio-025 has a high barrier for the selection of resistance. In Debio-025-treated patients, cyclophilin B (CypB) levels in peripheral blood mononuclear cells decreased from 67 +/- 6 (standard error) ng/mg protein (baseline) to 5 +/- 1 ng/mg protein at day 15 (P < 0.01). Conclusion: Debio-025 induced a strong drop in CypB levels, coinciding with the decrease in hepatitis C viral load. These are the first preliminary human data supporting the hypothesis that CypB may play an important role in hepatitis C virus replication and that Cyp inhibition is a valid target for the development of anti-hepatitis C drugs.
机译：Debio-025是一种口服亲环蛋白（Cyp）抑制剂，在体外具有有效的抗丙型肝炎病毒活性。在一项随机，双盲，安慰剂对照研究中，研究了其对病毒载量的影响以及对细胞内Cyp水平的影响。口服1200 mg每天两次，每天14次口服治疗14天后，丙型肝炎病毒的平均载量显着下降了3.6 log（10）（P <0.0001），对研究中代表的3个基因型（1、3和4）产生了影响。此外，在治疗过程中没有病毒反弹表明Debio-025对耐药性的选择有很高的障碍。在接受Debio-025治疗的患者中，第15天外周血单个核细胞中亲环蛋白B（CypB）的水平从67 +/- 6 ng / mg蛋白质（基线）降至5 +/- 1 ng / mg蛋白质（P <0.01）。结论：Debio-025诱导CypB水平强烈下降，与丙型肝炎病毒载量下降相吻合。这些是第一个初步的人类数据，支持以下假设：CypB可能在丙型肝炎病毒复制中起重要作用，而Cyp抑制是抗丙型肝炎药物开发的有效目标。

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