揭示了SARS-CoV-2进入宿主细胞的动态机制,在单个粒子水平
Siying Li1, Hui Yang2,3, Falin Tian4
1School of Chemistry and Life Science, Advanced Institute of Materials Science, Changchun University of Technology, Changchun 130012, China.
ACS nano
|October 1, 2024
概括
SARS-CoV-2 的 Omicron 变种比 Delta 或野生型更强烈地与 ACE2 受体结合. 奥米克龙还通过克拉依赖性内细胞分裂更快,更有效地进入细胞.
科学领域:
- 病毒学 病毒学
- 生物物理学的生物物理.
- 细胞生物学 细胞生物学
背景情况:
- 了解严重急性呼吸道冠状病毒2 (SARS-CoV-2) 细胞进入是COVID-19药物开发的关键.
- 病毒结合动态和病原体需要详细的研究.
研究的目的:
- 研究SARS-CoV-2结合细胞膜和进入机制的动态特征.
- 为了比较不同SARS-CoV-2变体的结合亲和和和进入动态,包括Omicron.
主要方法:
- 基于原子力显微镜 (AFM) 的单分子力光谱 (SMFS) 用于研究病毒-细胞膜相互作用.
- 使用实时力追踪和单粒子光追踪.
- 粗粒度分子动力学 (CGMD) 模拟用于参数分析.
主要成果:
- 奥米克朗变异病毒样颗粒 (VLPs) 对ACE2受体的结合亲和力比三角形和野生型 (WT) 强.
- SARS-CoV-2 VLP 进入细胞需要大约 200 ms 和 60 pN,与 CGMD 模拟保持一致.
- 奥米克朗变种表现出更高的细胞进入速度,更低的力,以及更高的概率,利用克拉素依赖性内细胞分裂.
结论:
- 该研究提供了对SARS-CoV-2 VLP入口的动态参数的定量见解.
- 奥米克龙变种表现出明显的,更高效的细胞入侵特征.
- 这些发现提供了针对SARS-CoV-2进入机制的潜在干预策略.
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