The recent spillover of SARS-CoV-2 in the human population resulted in the ongoing COVID-19 pandemic which has already caused 4.9 million infections and more than 326,000 fatalities. To initiate infection the SARS-CoV-2 spike (S) glycoprotein promotes attachment to the host cell surface, determining host and tissue tropism, and fusion of the viral and host membranes. Although SARS-CoV-2 S is the main target of neutralizing antibodies and the focus of vaccine design, its stability and conformational dynamics are limiting factors for developing countermeasures against this virus. We report here the design of a prefusion SARS-CoV-2 S ectodomain trimer construct covalently stabilized in the closed conformation. Structural and antigenicity analysis showed we successfully shut S in the closed state without otherwise altering its architecture. Finally, we show that this engineering strategy is applicable to other beta-coronavirus S glycoproteins and might become an important tool for vaccine design, structural biology, serology and immunology studies.

中文翻译：

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通过结构指导设计，关闭冠状病毒可加标糖蛋白。

SARS-CoV-2最近在人群中的扩散导致持续的COVID-19大流行，已造成490万例感染和326,000多例死亡。为了引发感染，SARS-CoV-2峰值（S）糖蛋白促进了对宿主细胞表面的附着，确定了宿主和组织的向性，以及病毒和宿主膜的融合。尽管SARS-CoV-2 S是中和抗体的主要目标和疫苗设计的重点，但其稳定性和构象动力学是制定针对该病毒的对策的限制因素。我们在这里报告共价稳定在封闭构象中的预融合SARS-CoV-2 S胞外域三聚体构建体的设计。结构和抗原性分析表明，我们成功关闭了S处于关闭状态，而没有改变其结构。最后，