预输形状中的2019-nCoV峰值的冷EM结构
Daniel Wrapp1, Nianshuang Wang1, Kizzmekia S Corbett2
1Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
概括
一种新型冠状病毒 (2019-nCoV) 的结构显示其尖端蛋白与SARS-CoV相比具有更高的亲缘关系. 这种结构性洞察对于开发有效的疫苗和治疗方法对抗2019-nCoV大流行至关重要.
科学领域:
- 病毒学
- 结构生物学
- 免疫学
背景情况:
- 2019新冠肺炎疫情对全球健康构成重大威胁.
- 冠状病毒尖峰 (S) 糖蛋白是医学对策的关键目标.
- 了解S蛋白的结构和功能对于抗击疫情至关重要.
研究的目的:
- 确定2019-nCoV S三元体的高分辨率结构.
- 研究2019-nCoV S与人类ACE2之间的结合相互作用.
- 评估2019-nCoV和SARS-CoV之间的潜在抗体交叉反应性.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 在3. 5安格斯特罗姆分辨率下确定S三元体结构.
- 使用生物物理方法分析了2019-nCoV S与ACE2的结合亲缘关系.
- 使用SARS-CoV RBD特异性单克隆抗体进行了结合性测试.
主要成果:
- 确定了2019-nCoV S三分体的3.5安格斯特罗姆冷EM结构.
- 一个主导状态显示一个受体结合域 (RBD) 在受体可访问的构造.
- 2019-nCoV S 与SARS-CoV S 相比,具有更高的亲和力结合人类血管激素转化酶2 (ACE2).
- 已发表的SARS-CoV RBD特异性单克隆抗体对2019-nCoV S的结合性有限.
结论:
- 确定2019-nCoV S蛋白质的结构为医疗对策的开发提供了基础.
- 对ACE2的更高的结合亲和力表明病毒进入的潜在机制.
- 有限的抗体交叉反应表明需要针对2019-nCoV的特定治疗策略.
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