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对蝙蝠冠状病毒ZXC21的受体结合域的结构洞察 ZXC21
Chenghai Wang1, Xiaoyan Nan1, Yang Deng2
1School of Biomedical Sciences, Hunan University, Changsha, Hunan, China.
蝙蝠冠状病毒ZXC21和ZC45与SARS-CoV-2具有很高的基因组相似性,但不结合人类的ACE2受体. 这项研究揭示了ZXC21受体结合域结构,为冠状病毒进化提供了洞察力.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 在COVID-19之前发现的蝙蝠冠状病毒ZXC21和ZC45具有与SARS-CoV-2显著的基因组同样性 (86%).
- 以前的研究表明,ZXC21和ZC45可能在SARS-CoV-2的出现中发挥了作用.
- ZXC21和ZC45的精确细胞入侵机制在很大程度上仍未被描述.
研究的目的:
- 阐明ZXC21受体结合域 (RBD) 的结构特征.
- 研究ZXC21 RBD与已知的人类冠状病毒受体的相互作用.
- 评估针对ZXC21.21的SARS-CoV-2向抗体的潜力.
主要方法:
- 确定了ZXC21受体结合域 (RBD) 的晶体结构.
- 使用表面等离子体共振 (SPR) 来测试ZXC21 RBD与人类冠状病毒受体 (ACE2,DPP4,APN,TMPRSS2) 之间的相互作用.
- 评估了P5S-3B11 Fab (SARS-CoV-2核心向抗体) 与ZXC21 RBD.的结合.
主要成果:
- ZXC21 RBD与其他β-冠状病毒RBD具有非常相似的核心结构,包括SARS-CoV-2.
- 与SARS-CoV-2相比,在ZXC21 RBD中观察到不同的受体结合动机 (RBM).
- ZXC21 RBD对人类ACE2,DPP4,APN或TMPRSS2.2没有表现出任何结合亲和力.
- P5S-3B11 Fab成功与ZXC21 RBD结合在一起.
结论:
- 对ZXC21 RBD的结构分析为了解其交互能力提供了基础.
- ZXC21不利用人类主要的冠状病毒入口受体,这表明细胞入侵途径不同.
- 一个SARS-CoV-2抗体与ZXC21 RBD的结合表明潜在的交叉中和,需要进一步调查其治疗含义.
- 这些发现有助于理解冠状病毒和SARS-CoV-2起源的进化格局.
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