ACE2受体加速,但在生物化学上不需要SARS-CoV-2膜融合
Marcos Cervantes1, Tobin Hess1, Giorgio G Morbioli1
1Departments of Molecular Physiology and Biomedical Engineering, University of Virginia Charlottesville VA 22908 USA kassonlab@gmail.com.
Chemical science
|June 30, 2023
概括
严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 可以与没有ACE2受体的细胞融合. ACE2加速融合,但不是必不可少的,这表明冠状病毒具有更广泛的宿主适应潜力.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- SARS-CoV-2病毒利用ACE2受体进入人类细胞.
- 关于ACE2在SARS-CoV-2膜融合中的作用仍在争论中,假设表明它既起着附着因子的作用,也起着尖端蛋白的 conformational 激活器的作用.
研究的目的:
- 直接测试ACE2是否在生化上是SARS-CoV-2-介导的膜融合所需的.
- 研究ACE2在病毒融合的动力学和机制中的特定作用.
主要方法:
- 利用DNA-脂质结合来创建合成附着因子,取代了ACE2.
- 用SARS-CoV-2伪病毒和类似病毒的粒子进行融合试验.
- 进行了动力分析,以确定膜融合中的速度限制步骤.
主要成果:
- 当一个合适的蛋白酶存在时,SARS-CoV-2伪病毒和类似病毒的粒子独立于ACE2实现了膜融合.
- 添加可溶性ACE2加速了聚变过程.
- ACE2的作用是双重的:在缺乏蛋白酶的情况下促进融合激活和随后的非激活.
- 动力学研究确定了ACE2依赖的和ACE2独立的速度限制步骤.
结论:
- 对于SARS-CoV-2的膜融合,ACE2不是一个严格的生化要求.
- 以其他因素替代ACE2的能力表明,SARS-CoV-2和相关冠状病毒的宿主进入机制更具适应性.
- 了解这些融合动态对于预测病毒进化和宿主热带性至关重要.
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