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刺途径抑制剂HhAntag通过GLI-S1PR轴抑制病毒感染

Jinyu Zhang¹, Chunsheng Dong², Zhiqiang Chen³

¹Jiangsu Key Laboratory of Infection and Immunity, Children's Hospital of Soochow University, Institute of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Suzhou 215123, China; Central Laboratory, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Cellular signalling

|April 16, 2025

概括

刺途径抑制剂HhAntag通过向GLI-S1PR轴,抑制病毒蛋白转化,显示广泛的抗病毒活性. 这一发现为各种病毒感染提供了潜在的新型抗病毒疗法.

科学领域:

病毒学病毒学
分子生物学分子生物学
药物发现药物发现药物发现

背景情况:

像Notch,Hedgehog (Hh) 和Wnt这样的信号通路与瘤发育,免疫反应和病毒感染有关.
这些途径和病毒病原体之间存在潜在的相互调节.

研究的目的:

为了选抗病毒性质的Notch,Hh和Wnt途径的抑制剂.
确定针对关键生物通路的新型抗病毒药物候选者.

主要方法:

对85种抑制剂对记者病毒 (VSV-GFP,DENV-Luc) 的查.
对HhAntag对多种病毒 (VSV,DENV,ZIKV,SFTSV) 的抗病毒活性评估.
分析GLI1的表达,病毒的附着,入口,转录和翻译.
用RNA测序来识别HhAntag.的分子标.

主要成果:

刺途径抑制剂HhAntag表现出广泛的抗病毒活性.
HhAntag通过降低GLI1的调节和特别阻断病毒蛋白转化来抑制病毒复制.
过度表达GLI1增强了病毒感染,而HhAntag治疗减少了斯芬戈-1-酸盐 (S1P) 受体表达 (S1PR1,S1PR5).
确定GLI-S1PR轴是HhAntag抗病毒作用的机制.

结论:

刺途径抑制剂,特别是HhAntag,具有显著的广泛抗病毒能力.
HhAntag通过通过GLI-S1PR轴抑制病毒蛋白转化而起作用.
这项研究强调了与瘤相关的Hh途径和病毒感染之间的联系,表明HhAntag是潜在的抗病毒疗法.

关键词:

GLI1 一个GLI1 一个这就是HhAntagtag.斯芬哥辛-1-酸盐 (S1P) 信号通路的受体信号.

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