Structure
Volume 28, Issue 11, 3 November 2020, Pages 1218-1224.e4
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Short Article
The Architecture of Inactivated SARS-CoV-2 with Postfusion Spikes Revealed by Cryo-EM and Cryo-ET

https://doi.org/10.1016/j.str.2020.10.001Get rights and content
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open access

Highlights

  • β-propiolactone-inactivated SARS-CoV-2 viruses display postfusion spikes

  • Cryo-ET structure of SARS-CoV-2 postfusion spikes was determined at 11 Å resolution

  • This study calls for crucial structural characterization of vaccine candidates

Summary

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.

Keywords

SARS-CoV-2
COVID-19
cryo-EM
cryo-ET
β-propiolactone-inactivated viruses
vaccine
spike
subtomogram averaging
postfusion
glycosylation

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These authors contributed equally