改变了SARS-CoV-2尖端蛋白突变体的 hACE2结合亲和力和S1/S2裂解效率,影响病毒细胞进入
Ke Wang1, Yu Pan2, Dianbing Wang2
1National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; Faculty of Synthetic Biology, Shenzhen Institute of Advanced Technology, Shenzhen, 518055, China; University of Chinese Academy of Sciences, Beijing, 100101, China.
Virologica Sinica
|June 21, 2023
概括
新的SARS-CoV-2变种在细胞进入上表现出不同的尖端蛋白效应. 这就是Omicron.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 流行病学 流行病学
背景情况:
- 新出现的SARS-CoV-2变种对感染控制构成挑战.
- 尖端蛋白突变影响病毒的进入,需要进行详细的比较.
研究的目的:
- 综合分析尖端蛋白突变对SARS-CoV-2变种的影响.
- 为了比较变体的尖峰表达,结合,进入效率和宿主细胞热带性.
主要方法:
- 研究了八种令人担忧 (VOC) 和感兴趣 (VOI) 的变体.
- 评估了使用伪病毒的尖端蛋白表达,蛋白质分解活性,与 hACE2 的结合亲和力,以及病毒进入效率.
- 研究了宿主细胞的热带性和TMPRSS2.2.的利用.
主要成果:
- 欧米克朗尖峰和RBD与hACE2的结合亲和力类似于野生类型.
- 阿尔法,贝塔,德尔塔和兰巴达伪病毒显示增强的细胞进入;Omicron显示轻微增加.
- 奥米克朗和Mu尖峰显示较低的S1/S2裂变和低效的TMPRSS2使用,表明细胞内的偏好.
- 所有变体都可能进入动物ACE2表达细胞,在动物中增加感染潜力,这表明病毒进化的潜在储库.
结论:
- 奥米克朗的高传播率与hACE2亲和关系无关,但可能是其他进入途径.
- 动物可能会成为SARS-CoV-2进化的储备体,因为它们的易感性增加了.
- 这些发现指导了流行病控制策略,并增强了对SARS-CoV-2演变的理解.
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