活性氧物种的促进推动了auranofin对E型肝炎病毒的抗病毒活性
Kateland Tiller1, S Tyler Williams1, Bo Wang1
1Virginia-Maryland College of Veterinary Medicine, Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Journal of virology
|December 9, 2025
概括
通过奥拉诺芬促进反应性氧物种 (ROS) 显示出对肝炎E病毒 (HEV) 的抗病毒活性. 联合奥拉诺芬和利巴维林治疗表现出协同效应,为HEV感染提供了潜在的新治疗策略.
科学领域:
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
- 宿主-病原体相互作用
背景情况:
- 肝炎E病毒 (HEV) 导致全球严重的感染,导致慢性肝炎,神经问题和不良妊娠结果.
- 目前用于HEV的治疗方法,利巴维林和基化干扰素,被非标签使用,并面临耐药性和毒性挑战.
- 对于新的,针对HEV的抗病毒疗法有极大需求.
研究的目的:
- 确定针对HEV的新型宿主导的抗病毒机制.
- 评估FDA批准的药物auranofin及其作用机制的抗病毒潜力.
- 探索奥拉诺芬与现有疗法结合的协同效应.
主要方法:
- 研究了auranofin对临床相关的HEV基因型和抗利巴维林耐药突变的抗病毒活性.
- 通过使用ROS抑制剂和D-氨基酸氧化酶,评估了活性氧物种 (ROS) 的作用.
- 分析了auranofin对与抗氧化剂和干扰素通路相关的宿主基因表达的影响.
- 在试验室中评估了auranofin和ribavirin联合治疗的协同抗病毒活性.
主要成果:
- 奥拉诺芬对HEV具有强大,剂量依赖的抗病毒活性,包括一种耐瑞巴维林菌株.
- 奥拉诺芬的抗病毒作用与ROS促进有机联系,因为抑制ROS会逆转其活性.
- D-氨基酸氧化酶还通过ROS产生抗HEV活性,证实ROS积累足以产生抗病毒作用.
- 奥拉诺芬治疗诱导了抗氧化剂,ER压力和干扰素刺激的基因表达,表明了抗病毒信号的激活.
- 与奥拉诺芬和利巴维林的联合治疗在体外表现出协同抗病毒活性.
结论:
- ROS促进是一种以前未被识别的针对HEV的宿主导抗病毒机制.
- 奥拉诺芬通过ROS诱导和主体抗病毒通路的激活有效地抑制HEV复制.
- 重新利用auranofin,单独或与利巴维林结合,为HEV感染提供了一个有前途的治疗策略.
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