Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
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DOI：
10.1126/science.abb2507
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发表时间：
2020-03-13
期刊：
影响因子：
56.9
通讯作者：
McLellan, Jason S.
中科院分区：
文献类型：
--
作者：
Wrapp, Daniel;Wang, Nianshuang;McLellan, Jason S.
一种新型冠状病毒(2019-nCoV)的暴发代表了一种已被宣布为国际关注的突发公共卫生事件的大流行威胁。冠状病毒尖峰蛋白(S)是疫苗、治疗性抗体和诊断的关键靶点。为了便于医学对策的开发，我们确定了2019年-nCoV S三聚体在预融合构象中的3.5埃分辨率的冷冻电子显微镜结构。三聚体的主要状态是三个受体结合域(RBD)中的一个向上旋转，形成受体可访问的构象。我们还提供了生物物理和结构证据表明，2019-nCoV S蛋白与血管紧张素转换酶2(ACE2)结合的亲和力高于严重急性呼吸综合征(SARS)-CoV S。此外，我们还测试了几种已发表的SARS-CoV RBD特异性单抗，发现它们与2019-NCoV S没有明显的结合，这表明两种RBD之间的抗体交叉反应可能是有限的。2019年-NCoV S的结构应该能够快速发展和评估应对当前公共卫生危机的医疗对策。
The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.