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The architecture of inactivated SARS-COV-2 with postfusion spikes revealed by cryo-EM and cryo-ET

DOI: 10.1016/j.str.2020.10.001 DOI Help

Authors: Chuang Liu (Southern University of Science and Technology,) , Luiza Mendonca (Wellcome Trust Centre for Human Genetics, University of Oxford) , Yang Yang (Shenzhen Third People's Hospital) , Yuanzhu Gao (Southern University of Science and Technology) , Chenguang Shen (Shenzhen Third People's Hospital) , Jiwei Liu (Wellcome Trust Centre for Human Genetics, University of Oxford) , Tao Ni (Wellcome Trust Centre for Human Genetics, University of Oxford) , 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 (Wellcome Trust Centre for Human Genetics, University of Oxford) , Weilong Liu (Shenzhen Third People's Hospital) , Shuman Xu (University of Science and Technology) , Yingxia Liu (Shenzhen Third People's Hospital; 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 (Shenzhen Third People's Hospital; Southern University of Science and Technology) , Lei Li (Shenzhen Third People's Hospital; Southern University of Science and Technology) , Peiyi Wang (Southern University of Science and Technology; Southern University of Science and Technology) , Peijun Zhang (Diamond Light Source; Wellcome Trust Centre for Human Genetics, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure

State: Published (Approved)
Published: October 2020

Open Access Open Access

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.

Journal Keywords: SARS-CoV-2; COVID-19; cryo-EM; cryo-ETβ-propiolactone-inactivated viruses; vaccine; spike; subtomogram averaging; postfusion; glycosylation

Subject Areas: Biology and Bio-materials, Medicine

Facility: cryo-EM center and the BSL-3 laboratory of the Second Affiliated Hospital, School of Medicine, in South University of Science and Technology

Documents:
1-s2.0-S0969212620303725-main.pdf