Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein
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DOI：
10.1016/j.cell.2020.02.058
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发表时间：
2020-04-16
期刊：
影响因子：
64.5
通讯作者：
Veesler, David
中科院分区：
文献类型：
--
作者：
Walls, Alexandra C.;Park, Young-Jun;Veesler, David
SARS-COV-2的出现导致> 90,000次感染和3,000人死亡。冠状病毒尖峰（S）糖蛋白促进进入细胞，是抗体的主要靶标。我们表明，SARS-COV-2 S使用ACE2进入细胞，并且SARS-COV-2 S和SARS-COV的受体结合结构域与与人ACE2相似的亲密关系结合，与人类在人类之间的有效传播相关。我们发现，SARS-COV-2 S糖蛋白在S-1/S-2亚基之间的边界上设有一个脂蛋白裂解位点，该部位在生物发生过程中进行了处理，并将该病毒与SARS-COV和与SARS相关的COV分开。我们确定了SARS-COV-2 S胞外域三聚体的冷冻EM结构，为疫苗和病毒进入的抑制剂设计提供了蓝图。最后，我们证明了SARS-COV S鼠多克隆抗体有效抑制SARS-COV-2 S介导的细胞中介导的进入细胞，表明靶向保守的S表位的交叉中和抗体可以在疫苗接种后引起。
The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S-1/S-2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.