Structure of the nCoV trimeric spike The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. Science, this issue p. 1260 The overall structure of the 2019-nCoV spike (S) protein resembles that of SARS-CoV S, but 2019-nCoV S binds more tightly to the host receptor. 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.

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融合前构象中 2019-nCoV 尖峰的冷冻电镜结构

nCoV 三聚体尖峰的结构世界卫生组织已宣布新型冠状病毒 (2019-nCoV) 的爆发为国际关注的突发公共卫生事件。该病毒通过其三聚体刺突糖蛋白与宿主细胞结合，使该蛋白成为潜在治疗和诊断的关键目标。瓦普等人。通过冷冻电子显微镜确定了 2019-nCoV 三聚体刺突蛋白的 3.5 埃分辨率结构。作者使用生物物理分析表明，这种蛋白质与其共同宿主细胞受体的结合比严重急性呼吸系统综合症 (SARS)-CoV 的相应刺突蛋白高至少 10 倍。他们还测试了三种已知与 SARS-CoV 刺突蛋白结合的抗体，但没有检测到与 2019-nCoV 刺突蛋白的结合。这些研究为指导 2019-nCoV 医学对策的制定提供了宝贵的信息。科学，这个问题 p。1260 2019-nCoV 刺突 (S) 蛋白的整体结构类似于 SARS-CoV S，但 2019-nCoV S 与宿主受体的结合更紧密。新型冠状病毒 (2019-nCoV) 的爆发代表了一种大流行威胁，已被宣布为国际关注的突发公共卫生事件。CoV 刺突 (S) 糖蛋白是疫苗、治疗性抗体和诊断的关键目标。为了促进医学对策的发展，我们确定了融合前构象中 2019-nCoV S 三聚体的 3.5 埃分辨率低温电子显微镜结构。三聚体的主要状态具有三个受体结合域 (RBD) 之一，以受体可接近的构象向上旋转。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) 的结合比严重急性呼吸系统综合症 (SARS)-CoV S 具有更高的亲和力。此外，我们测试了几种已发表的 SARS-CoV RBD-特异性单克隆抗体，发现它们与 2019-nCoV S 没有明显的结合，这表明抗体交叉反应性可能在两个 RBD 之间受到限制。2019-nCoV S 的结构应该能够快速开发和评估医疗对策，以解决持续的公共卫生危机。我们测试了几种已发表的 SARS-CoV RBD 特异性单克隆抗体，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性可能受到限制。2019-nCoV S 的结构应该能够快速开发和评估医疗对策，以解决持续的公共卫生危机。我们测试了几种已发表的 SARS-CoV RBD 特异性单克隆抗体，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性可能受到限制。2019-nCoV S 的结构应该能够快速开发和评估医疗对策，以解决持续的公共卫生危机。