Structures and distributions of SARS-CoV-2 spike proteins on intact virions

Nature. 2020 Dec;588(7838):498-502. doi: 10.1038/s41586-020-2665-2. Epub 2020 Aug 17.


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude1. Heavily glycosylated S trimers bind to the angiotensin-converting enzyme 2 receptor and mediate entry of virions into target cells2-6. S exhibits extensive conformational flexibility: it modulates exposure of its receptor-binding site and subsequently undergoes complete structural rearrangement to drive fusion of viral and cellular membranes2,7,8. The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy2,7,9-12, but the structure and distribution of S on the virion surface remain unknown. Here we applied cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions and determine the high-resolution structure, conformational flexibility and distribution of S trimers in situ on the virion surface. These results reveal the conformations of S on the virion, and provide a basis from which to understand interactions between S and neutralizing antibodies during infection or vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology
  • COVID-19 / immunology
  • COVID-19 Vaccines / immunology
  • Cell Line, Tumor
  • Cryoelectron Microscopy*
  • Humans
  • Models, Molecular
  • Pliability
  • Protein Conformation
  • Protein Multimerization
  • SARS-CoV-2 / chemistry
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism*
  • SARS-CoV-2 / ultrastructure*
  • Spike Glycoprotein, Coronavirus / analysis*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / isolation & purification
  • Spike Glycoprotein, Coronavirus / ultrastructure*
  • Virion / chemistry*
  • Virion / isolation & purification
  • Virion / metabolism
  • Virion / ultrastructure*


  • Antibodies, Neutralizing
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2