质子激活的化物通道抑制了SARS-CoV-2尖端蛋白介导的病毒通过内分体通路进入
Nicholas Koylass1, Jaiprasath Sachithanandham2, James Osei-Owusu1
1Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Journal of cellular physiology
|July 23, 2025
概括
质子激活化物 (PAC) 通道通过调节内体酸度来抑制SARS-CoV-2的进入. 过度表达的PAC阻断了病毒的进入,这表明它是病毒.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 通过内细胞酶酶进入细胞,这一过程依赖于内体酸性化.
- 质子 (V-ATPase) 驱动酸化,而化物载体调节质子梯度.
- 质子激活化物 (PAC) 通道最近被确定为内体 pH 的调节器.
研究的目的:
- 调查PAC通道在SARS-CoV-2病毒进入中的作用.
- 为了确定PAC是否可以成为针对SARS-CoV-2感染的治疗点.
主要方法:
- 在表达ACE2的HEK 293T细胞中PAC的过度表达.
- 伪病毒进入试验.
- 对内体酸性化和局部化的分析.
- 使用甲素抑制剂 (E64-d) 和TMPRSS2表达的抑制试验.
- 在Vero E6细胞中使用活的SARS-CoV-2分离物 (B.1和Omicron XBB.1.16) 进行斑块检测.
主要成果:
- PAC过度表达显著抑制了SARS-CoV-2尖端介导的病毒进入.
- PAC的抑制作用取决于其内体局部化和通道活性.
- 抑制机制涉及抑制内体进入途径,类似于甲素抑制.
- PAC过度表达减少了活体SARS-CoV-2分离体的斑块形成.
结论:
- 该PAC通道是SARS-CoV-2进入的关键抑制剂.
- 通过负面调节内体酸性化来发挥PAC的功能.
- PAC代表了SARS-CoV-2和其他利用内体路径的病毒的潜在新疗法标.
关键词:
在TMEM206中使用.在 cathepsin 中.内部体内体内体内体内体内体内体内体内体内体内体内质子激活化物通道 (PAC)严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2)通过膜的血清蛋白酶2 (TMPRSS2)更多相关视频
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