血管内皮生长因子受体2作为抑制肠道病毒复制的潜在宿主目标
Xiaoyu Zhao1,2, Rui Qiao2, Meng Hao3
1Shanghai Sci-Tech Inno Center for Infection & Immunity, National Medical Center for Infectious Diseases, Huashan Hospital, Institute of Infection and Health, Fudan University, Shanghai, China.
Journal of virology
|September 17, 2024
概括
帕佐帕尼布有效抑制肠道病毒A71 (EV-A71) 复制,并表现出广泛的抗肠道病毒活性. 血管内皮生长因子受体2 (VEGFR2) 被确定为一种对EV-A71复制至关重要的新型宿主因子.
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:
- 肠道病毒A71 (EV-A71) 导致手足口病 (HFMD),并对公众健康构成重大威胁.
- 对肠道病毒的现有抗病毒疗法是有限的,需要识别新的治疗点和药剂.
- 主体激酶是病毒复制的关键调节者,使他们成为抗病毒药物开发的潜在目标.
研究的目的:
- 确定抑制EV-A71复制的宿主因子和小分子.
- 研究血管内皮生长因子受体2 (VEGFR2) 在EV-A71感染中的作用.
- 评估已识别的化合物对各种肠道病毒的广泛抗病毒活性.
主要方法:
- 激酶抑制剂图书馆选使用拉布多米索尔科马细胞和人类肠道器官.
- 对EV-A71和其他肠道病毒的抗病毒活性测定.
- 进行VEGFR2敲击和过度表达的实验.
- 转录组分析以阐明下游的信号通路.
主要成果:
- 帕佐帕尼布是一种血管内皮生长因子受体 (VEGFR) 抑制剂,强烈抑制了具有高选择性指数的EV-A71复制.
- 帕佐帕尼布对CVA10,CVB1,EV-D70和HRV-A具有广泛的抗肠道病毒活性.
- VEGFR2被确定为EV-A71复制的新型宿主依赖因子,其敲击抑制和过度表达促进病毒复制.
- 转录组分析表明,VEGFR2通过TSAd-Src-PI3K-Akt通路对抗EV-A71感染.
结论:
- 帕佐帕尼布是一种有前途的广谱抗肠道病毒治疗候选药物.
- VEGFR2是EV-A71复制的关键宿主因子,也是潜在的治疗点.
- 向VEGFR2及其相关途径为开发抗肠道病毒疗法提供了一种新的策略.
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