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通过FDA批准的RdRp抑制剂抑制HEV复制

Preeti Hooda¹, Mohammed Al-Dosari², Neha Sinha³

¹Virology Lab, Department of Life Sciences, Shiv Nadar Institute of Eminence, Gautam Budh Nagar 201314, India.

|November 16, 2023

概括

费维皮拉维尔和索福斯布维尔在治疗E型肝炎病毒 (HEV) 感染方面表现有前途,通过抑制病毒RNA依赖RNA聚合酶. 组合疗法显著减少了病毒RNA,这表明法维皮拉维尔是一种潜在的抗HEV药物.

科学领域:

病毒学病毒学
肝病学肝病学是一种肝病学.
药物发现药物发现药物发现

背景情况:

肝炎E病毒 (HEV) 引起急性和慢性肝炎,慢性病例的治疗选择有限.
目前慢性HEV的治疗方法包括基化干扰素α和利巴维林.
病毒RNA依赖RNA聚合酶 (RdRp) 对于HEV复制和潜在的抗病毒标至关重要.

研究的目的:

选已知RNA-依赖RNA聚合酶 (RdRp) 抑制分子的抗HEV活性.
评估法维皮拉维尔和索福斯布维尔作为单疗法和联合治疗对HEV的疗效.
确定用于治疗乙型肝炎的有前途的抗病毒药物.

主要方法:

对RdRp抑制剂的查:法维皮拉维尔,索福斯布维尔,雷德西维尔,菲利布维尔和特戈布维尔.
对所选化合物的RdRp抑制活性 (IC50值) 的体外评估.
通过测量病毒RNA拷贝数来评估组合疗法的疗效.

主要成果:

费维皮拉维尔和索福斯布维尔显著抑制了HEV RdRp活性,IC50值分别为10.2 ± 4.9 μM和5.2 ± 2.9 μM.
利巴维林作为参考药物,其IC50为3.5±1.6μM.
与法维皮拉维尔和索福斯布维尔的联合治疗使病毒RNA拷贝数量减少了约90%,表明了附加效应.

结论:

费维皮拉维尔和索福斯布维尔是HEV RdRp的有效抑制剂.
费维皮拉维尔和索福斯布维尔的联合治疗显示出治疗肝炎E的显著潜力.
费维皮拉维尔是作为抗HEV治疗剂进一步开发的有希望的候选药物,特别是在组合疗法中.

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