Cryo-EM structure of a SARS-CoV-2 omicron spike protein ectodomain

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66 Scopus citations


The omicron variant of SARS-CoV-2 has been spreading rapidly across the globe. The virus-surface spike protein plays a critical role in the cell entry and immune evasion of SARS-CoV-2. Here we determined the 3.0 Å cryo-EM structure of the omicron spike protein ectodomain. In contrast to the original strain of SARS-CoV-2 where the receptor-binding domain (RBD) of the spike protein takes a mixture of open (“standing up”) and closed (“lying down”) conformations, the omicron spike molecules are predominantly in the open conformation, with one upright RBD ready for receptor binding. The open conformation of the omicron spike is stabilized by enhanced inter-domain and inter-subunit packing, which involves new mutations in the omicron strain. Moreover, the omicron spike has undergone extensive mutations in RBD regions where known neutralizing antibodies target, allowing the omicron variant to escape immune surveillance aimed at the original viral strain. The stable open conformation of the omicron spike sheds light on the cell entry and immune evasion mechanisms of the omicron variant.
Original languageEnglish (US)
Article number1214
Pages (from-to)1214
Number of pages1
JournalNature Communications
Issue number1
StatePublished - Dec 2022

Bibliographical note

Funding Information:
We thank Wei Zhang for site-directed mutagenesis of the SARS-CoV-2 spike gene, Wei Shi for negative stain EM and vitrobot preparations, and the staff at the cryo-EM facility and instrument core facility in the Hormel Institute, University of Minnesota. This work was supported by the start-up funding (to B.L.) from the Hormel Institute, University of Minnesota, and by NIH grants R01AI089728 and R01AI110700 (to F.L.).

Publisher Copyright:
© 2022, The Author(s).


  • COVID-19
  • cell entry
  • cryo-EM
  • immune evasion
  • receptor-binding domain

PubMed: MeSH publication types

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


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