美国得克萨斯大学奥斯汀分校Jason S. McLellan等研究人员报道了2019-nCoV突刺蛋白预融合构象下的冷冻电镜结构。该研究于2020年2月19日在线发表于国际一流学术期刊《科学》。

研究人员报道了处于预融合构象的2019-nCoV突刺蛋白三聚体的冷冻电镜（cryo-EM）结构，其分辨率为3.5Å。三聚体的主要状态为三个受体结合结构域（RBD）之一向上旋转为受体可及构象。

研究人员还报道了相关的生物物理和结构证据，与SARS-CoV突刺蛋白相比，2019-nCoV突刺蛋白能够以更高的亲和力结合ACE2受体。研究人员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突刺蛋白没有明显的结合，这表明两种病毒RBD之间的抗体交叉反应性可能受到限制。因此，2019-nCoV突刺蛋白的cyro-EM结构能够促进相关医疗对策的开发，从而解决目前的全球公共卫生危机。

新型β冠状病毒（2019-nCov）的爆发逐渐变为大规模的流行威胁，目前已被世界卫生组织（WHO）宣布为国际公共卫生紧急事件（PHEIC）。CoV突刺（S）糖蛋白是疫苗、治疗性抗体和诊断方法的关键靶标。

附；英文原文

Title: Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Author: Daniel Wrapp, Nianshuang Wang, Kizzmekia S. Corbett, Jory A. Goldsmith, Ching-Lin Hsieh, Olubukola Abiona, Barney S. Graham, Jason S. McLellan

Issue&Volume: 2020/02/19

Abstract: AbstractThe outbreak of a novel betacoronavirus (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 (MCM) development, we determined a 3.5 -resolution cryo-EM 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 show biophysical and structural evidence that the 2019-nCoV S binds ACE2 with higher affinity than 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 antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.

DOI: 10.1126/science.abb2507

Source: https://science.sciencemag.org/content/early/2020/02/19/science.abb2507