对尖端激活和宿主蛋白酶利用的结构和功能约束限制了与SARS-CoV-2相关的蝙蝠冠状病毒的细胞进入
Qingqing Li1, Xiao Cai1, Xiaoning Li2
1Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Journal of virology
|July 24, 2025
概括
研究BANAL-52和BANAL-103冠状病毒揭示了结构和蛋白酶障碍,限制了动物感染潜力. SARS-CoV-2康复血清中和了这些相关病毒,这表明广谱疗法的抗原性得到保护.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- 野生动物中与SARS-CoV-2 (SC2r-CoVs) 相关的冠状病毒构成了动物传播的威胁.
- 尖 (S) 蛋白质特征和细胞进入机制决定了跨物种的感染性.
- 在遗传上,BANAL-52和BANAL-103与SARS-CoV-2最接近,这使得它们成为研究病毒进入的关键模型.
研究的目的:
- 为了研究BANAL-52和BANAL-103尖端蛋白的分子约束.
- 将它们的S介导细胞进入机制与SARS-CoV-2进行比较.
- 评估它们的动物感染潜力和抗原性质.
主要方法:
- 低温电子显微镜 (Cryo-EM) 用于确定尖结构.
- 位点定向的突变发生以探测S形状转换.
- 使用SARS-CoV-2康复血清进行伪病毒中和试验.
- 对病毒进入宿主蛋白酶利用的分析.
主要成果:
- 班纳尔尖峰显示ACE2结合减少和明显的"锁定"或"关闭"形状,由脂质和甘氨酸稳定.
- BANAL尖端主要利用了溶酶蛋白酶,与SARS-CoV-2的更广泛的蛋白酶使用不同.
- 引入一种素裂解部位增强了BANAL尖峰的融合性.
- SARS-CoV-2康复血清中和了BANAL伪病毒,表明抗原性得到保护.
结论:
- 班纳尔刺的结构和蛋白质分解特征对动物传播构成障碍.
- 保存的抗原性表明,对新出现的SC2r-CoVs有潜在的广泛疗法.
- 建议采取有针对性的监测策略来监测野生动物中的SC2r-CoVs.
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