对于SARS-CoV-2 BA.2.86和JN.1亚变种的进化和抗体逃避的结构基础
Haonan Yang1, Huimin Guo2, Aojie Wang1,3
1Department of Biochemistry, Key University Laboratory of Metabolism and Health of Guangdong, School of Medicine, Institute for Biological Electron Microscopy, Southern University of Science and Technology, Shenzhen, Guangdong Province, China.
Nature communications
|September 4, 2024
概括
新的SARS-CoV-2 Omicron亚型BA.2.86和JN.1显示出抗体逃避的增加. 结构分析揭示了这些变异中的突变如何影响它们与ACE2受体和抗体的相互作用.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 目前的COVID-19大流行是由快速演变的SARS-CoV-2 Omicron亚型驱动的.
- BA.2.86及其后代JN.1表现出显著的突变,特别是在Spike (S) 蛋白中,引发了人们对增加的传染性和免疫逃避的担忧.
研究的目的:
- 系统地调查SARS-CoV-2 Omicron亚型BA.2.86和JN.1.的中和易感性.
- 阐明这些新兴变异中增强抗体逃避和改变病毒受体相互作用的结构基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 确定了与人类ACE2受体结合的BA.2.86和JN.1尖端蛋白的结构.
- 进行了中和试验,以评估这些亚变体对抗体的敏感性.
- 结构分析侧重于受体结合域 (RBD) 内的突变及其对ACE2结合和抗体识别的影响.
主要成果:
- 与之前的Omicron变种相比,BA.2.86和JN.1显示出增强的抗体逃避能力.
- 化EM结构显示,BA.2.86和JN.1 RBD中的突变重塑了RBD-ACE2相互作用网络.
- 在JN.1中的L455S突变显著改变了RBD-ACE2接口,表明与BA.2.86.6.2相比,结合亲和力降低了.
- 对大致中和抗体的分析确定了BA.2.86.6所使用的免疫逃避机制.
结论:
- SARS-CoV-2 Omicron亚型BA.2.86和JN.1具有显著的突变,增强它们逃避免疫反应的能力.
- 对RBD-ACE2相互作用的结构洞察力为这些循环变体的进化和免疫逃脱特性提供了机械的理解.
- 了解Omicron亚型的进化格局对于开发有效的抗击措施对抗COVID-19至关重要.
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