Characterization of the SARS-CoV-2 Spike in an Early Prefusion Conformation

Li, Tingting; Zheng, Qingbing; Yu, Hai; Wu, Dinghui; Xue, Wenhui; Zhang, Yuyun; Huang, Xiaofen; Zhou, Lizhi; Zhang, Zhigang; Zha, Zhenghui; Chen, Tingting; Wang, Zhiping; Chen, Jie; Sun, Hui; Deng, Tingting; Wang, Yingbin; Chen, Yixin; Zhao, Qinjian; Zhang, Jun; Gu, Ying; Li, Shaowei; Xia, Ningshao

Pandemic coronavirus disease 2019 (COVID-19) is caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there are no efficacious vaccines or therapeutics that are urgently needed. We expressed three versions of spike (S) proteins—receptor binding domain (RBD), S1 subunit and S ectodomain—in insect cells. RBD appears monomer in solutions, whereas S1 and S associate into homotrimer with substantial glycosylation. The three proteins confer excellent antigenicity with six convalescent COVID-19 patient sera. Cryo-electron microscopy (cryo-EM) analyses indicate that the SARS-CoV-2 S trimer dominate in a unique conformation distinguished from the classic prefusion conformation of coronaviruses by the upper S1 region at lower position ~15 Å proximal to viral membrane. Such conformation is proposed as an early prefusion state for the SARS-CoV-2 spike that may broaden the knowledge of coronavirus and facilitate vaccine development.