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

Chuang Liu(Southern University of Science and Technology), Luiza Mendonça(Centre for Human Genetics), Yang Yang(Shenzhen Third People’s Hospital), Yuanzhu Gao(Southern University of Science and Technology), Chenguang Shen(Shenzhen Third People’s Hospital), Jiwei Liu(Centre for Human Genetics), Tao Ni(Centre for Human Genetics), Bin Ju(Shenzhen Third People’s Hospital), Congcong Liu(Southern University of Science and Technology), Xian Tang(Shenzhen Third People’s Hospital), Jinli Wei(Shenzhen Third People’s Hospital), Xiaomin Ma(Southern University of Science and Technology), Yanan Zhu(Centre for Human Genetics), Weilong Liu(Shenzhen Third People’s Hospital), Shuman Xu(Southern University of Science and Technology), Yingxia Liu(Southern University of Science and Technology), Jing Yuan(Shenzhen Third People’s Hospital), Jing Wu(Southern University of Science and Technology), Zheng Liu(Southern University of Science and Technology), Zheng Zhang(Southern University of Science and Technology), Lei Liu(Southern University of Science and Technology), Peiyi Wang(Southern University of Science and Technology), Peijun Zhang(Centre for Human Genetics)
Structure
October 14, 2020
10.1016/j.str.2020.10.001
Cited by 205Open Access
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Abstract

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.

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