SARS-CoV-2 异常地提升了线粒体的生物能量,以诱导强大的病毒传播
Hye Jin Shin1,2, Wooseong Lee1, Keun Bon Ku1
1Department of Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea.
Signal transduction and targeted therapy
|May 11, 2024
概括
严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 感染会提高线粒体的能量产生,并激活EGFR信号. 药物vandetanib针对这些途径,减少病毒传播和小鼠的炎症.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 导致显著的多器官损伤,但其细胞效应仍然不清楚.
- 了解SARS-CoV-2对细胞过程的影响对于开发有效的治疗方法至关重要.
研究的目的:
- 调查SARS-CoV-2诱导的细胞变化,特别关注线粒体功能和EGFR信号传递.
- 为 COVID-19 确定潜在的宿主向疗法.
主要方法:
- 在SARS-CoV-2感染细胞中分析线粒体的生物能量和EGFR信号.
- 对EGFR抑制剂治疗后的病毒传播和细胞变化的评估.
- 在 SARS-CoV-2 感染 hACE2 转基因小鼠中评估范德坦尼布的疗效.
主要成果:
- SARS-CoV-2 感染异常增加了线粒体的跨膜潜力,促进了线粒体的延长,并增强了氧化酸化 (OXPHOS) 和 ATP 生产.
- 病毒激活EGFR信号级联,导致线粒体EGFR贩运,从而支持病毒的传播.
- 范德特尼布治疗通过抑制EGFR流入线粒体并恢复正常的OXPHOS和ATP水平,减少了SARS-CoV-2的传播.
- 范德特尼布在感染的小鼠中减轻了肺炎和减少病毒载量,并对SARS-CoV-2变种表现出广泛的疗效.
结论:
- 在感染初期,SARS-CoV-2 破坏了线粒体动力学和EGFR贩运,这对病毒传播至关重要.
- EGFR代表了对抗COVID-19的抗病毒疗法的有前途的宿主标.
- 范德特尼布显示出作为抗病毒剂对抗SARS-CoV-2及其变种的显著潜力.
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