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

Structure. 2020 Nov 3;28(11):1218-1224.e4. doi: 10.1016/j.str.2020.10.001. Epub 2020 Oct 15.


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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Betacoronavirus / drug effects
  • Betacoronavirus / immunology
  • Betacoronavirus / ultrastructure*
  • COVID-19 Vaccines
  • Chlorocebus aethiops
  • Coronavirus Infections / immunology
  • Coronavirus Infections / prevention & control
  • Cryoelectron Microscopy
  • Disinfectants / pharmacology*
  • Electron Microscope Tomography
  • Humans
  • Propiolactone / pharmacology*
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / ultrastructure
  • Vaccines, Inactivated / immunology
  • Vero Cells
  • Viral Vaccines / immunology
  • Virion / drug effects*
  • Virion / ultrastructure


  • COVID-19 Vaccines
  • Disinfectants
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Inactivated
  • Viral Vaccines
  • spike glycoprotein, SARS-CoV
  • Propiolactone