针对宿主的化合物peruvoside对积极感应RNA病毒具有广泛的抗病毒活性
Kan Xing Wu1, Thinesshwary Yogarajah2,3, Marcus Wing Choy Loe2
1Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore.
Acta pharmaceutica Sinica. B
|May 30, 2023
概括
抗病毒酸通过酸化高尔基特异性brefeldin A-耐药瓜宁核酸交换因子1 (GBF1) 来限制病毒工厂,从而提供对宿主导向的保护,防止积极感应的RNA病毒.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 积极感官RNA病毒利用病毒工厂,膜结合器官,进行复制.
- 这些工厂集中病毒和细胞因子,对于病毒传播至关重要.
- 调节细胞内储存,内网和戈尔吉装置是工厂形成的关键.
研究的目的:
- 为了研究广泛的抗病毒药物peruvoside的机制.
- 为了确定peruvoside如何影响病毒工厂的形成.
- 探索peruvoside作为一种潜在的宿主导抗病毒疗法.
主要方法:
- 研究了维oside对病毒工厂形成的影响.
- 分析了激酶信号通路,包括Src,PLC,循环素依赖激酶1和ERK1/2.2.
- 检查了戈尔吉特异性的brefeldin A-耐药性瓜宁核酸交换因子1 (GBF1) 酸化和局部化.
- 在小鼠模型中评估peruvoside的疗效.
主要成果:
- 佩鲁维oside通过诱导戈尔吉特异性GBF1酸化来限制病毒工厂的形成.
- 这种酸化导致GBF1剥夺和下游抗病毒信号的激活.
- 信号传递涉及Src,PLC,循环素依赖激酶1和ERK1/2通路,针对GBF1在Threonine 1337中的目标.
- 佩鲁维oside在小鼠中显示出100%的保护,病毒标位降低,无细胞毒性.
结论:
- 珀鲁伏通过破坏病毒工厂,充当宿主导的抗病毒剂.
- 该机制涉及有针对性的GBF1酸化,影响病毒复制.
- 珀鲁伏作为治疗积极感应RNA病毒感染的治疗剂具有前景.
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