通过基于报告病毒的高通量查,对日本脑炎病毒感染的新型抗病毒发现
Chunhong Yin1,2, Peipei Yang1,3, Qingcui Xiao4
1State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Journal of medical virology
|January 18, 2024
概括
日本脑炎 (JE) 是一个全球性的健康威胁,缺乏具体的治疗方法. 研究人员发现,现有的药物塞法兰丁有效抑制了JE病毒的复制,并减轻了小鼠的感染.
科学领域:
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
- 公共卫生 公共卫生
背景情况:
- 日本脑炎 (JE) 构成了全球重大公共卫生挑战.
- 目前对JE的治疗选择有限,没有批准的特定抗病毒药物.
- 现有的疫苗可能无法到达所有面临风险的人群,这凸显了需要新的治疗策略.
研究的目的:
- 开发一种高通量查 (HTS) 系统,用于识别潜在的抗日本脑炎病毒 (JEV) 药物.
- 发现用于治疗JE的新药候选药物.
- 调查已识别的化合物的作用机制.
主要方法:
- 使用纳米化酶 (Nluc) 开发一个高内容的JEV报告员系统.
- 一个商业抗病毒库的高通量查 (HTS) 针对JEV.
- 作用研究的机制,包括抑制JEVRNA依赖RNA聚合酶.
- 在JEV感染的小鼠模型中进行体内疗效测试.
主要成果:
- 通过HTS识别了5种具有针对JEV显著抗病毒活性的药物.
- 发现塞法兰丁通过阻断GTP与病毒RNA依赖RNA聚合酶结合,直接抑制JEV复制.
- 用塞法兰丁治疗在小鼠模型中证明有效缓解JEV感染.
结论:
- 塞法兰作为日本脑炎的潜在治疗剂显示出希望.
- 开发的HTS系统是快速发现抗病毒药物的有效工具.
- 为了临床开发,需要进一步研究西法兰丁的抗JEV活性.
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