The Architecture of Inactivated SARS-CoV-2 with Postfusion Spikes Revealed by Cryo-EM and Cryo-ET

Liu, Chuang; Mendonça, Luiza; Yang, Yang; Gao, Yuanzhu; Shen, Chenguang; Liu, Jiwei; Ni, Tao; Ju, Bin; Liu, Congcong; Tang, Xian; Wei, Jinli; Ma, Xiaomin; Zhu, Yanan; Liu, Weilong; Xu, Shuman; Liu, Yingxia; Yuan, Jing; Wu, Jing; Liu, Zheng; Zhang, Zheng; Liu, Lei; Wang, Peiyi; Zhang, Peijun

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) resulted from the outbreak of SARS-CoV-2 in December 2019. Currently, multiple efforts are being made to rapidly develop vaccines and treatments to fight COVID-19. Current vaccine candidates use inactivated SARS-CoV-2 viruses; therefore, it is important to understand the architecture of inactivated SARS-CoV-2. We have genetically and structurally characterized β-propiolactone-inactivated viruses from a propagated and purified clinical strain of SARS-CoV-2. We observed that the virus particles are roughly spherical or moderately pleiomorphic. Although a small fraction of prefusion spikes are found, most spikes appear nail shaped, thus resembling a postfusion state, where the S1 protein of the spike has disassociated from S2. Cryoelectron tomography and subtomogram averaging of these spikes yielded a density map that closely matches the overall structure of the SARS-CoV postfusion spike and its corresponding glycosylation site. Our findings have major implications for SARS-CoV-2 vaccine design, especially those using inactivated viruses.