Cell Reports
Volume 39, Issue 4, 26 April 2022, 110729
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Article
Structural and functional impact by SARS-CoV-2 Omicron spike mutations

https://doi.org/10.1016/j.celrep.2022.110729Get rights and content
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Highlights

  • Omicron spike requires a high level of ACE2 for efficient membrane fusion

  • Mutations in Omicron remodel the antigenic surfaces of the spike trimer

  • Excessive mutations may have compromised fusogenic capability of Omicron spike

Summary

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), bearing an unusually high number of mutations, has become a dominant strain in many countries within several weeks. We report here structural, functional, and antigenic properties of its full-length spike (S) protein with a native sequence in comparison with those of previously prevalent variants. Omicron S requires a substantially higher level of host receptor ACE2 for efficient membrane fusion than other variants, possibly explaining its unexpected cellular tropism. Mutations not only remodel the antigenic structure of the N-terminal domain of the S protein but also alter the surface of the receptor-binding domain in a way not seen in other variants, consistent with its remarkable resistance to neutralizing antibodies. These results suggest that Omicron S has acquired an extraordinary ability to evade host immunity by excessive mutations, which also compromise its fusogenic capability.

Keywords

SARS-CoV-2
spike protein
cryo-EM
structure

Research topic(s)

CP: Molecular biology

Data and code availability

  • The atomic structure coordinates have been deposited in the RCSB Protein DataBank (PDB) under the accession numbers PDB: 7TNW and PDB: 7TO4 and the electron microscopy maps deposited in the Electron Microscopy DataBank (EMDB) under the accession numbers EMDB: EMD-26021 and EMDB: EMD-26029, and they are publicly available. These accession numbers are also listed in the key resources table.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

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Present address: GV20 Therapeutics LLC, 1 Broadway Floor 14, Cambridge, MA 02142, USA

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These authors contributed equally

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Lead contact