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Review
. 2025 Jul;23(7):455-468.
doi: 10.1038/s41579-025-01185-8. Epub 2025 May 6.

SARS-CoV-2 spike protein: structure, viral entry and variants

Bing Chen  1 , Michael Farzan  2   3 , Hyeryun Choe  4
Affiliations
Review

SARS-CoV-2 spike protein: structure, viral entry and variants

Bing Chen et al. Nat Rev Microbiol. 2025 Jul.

Abstract

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a devastating global pandemic for 4 years and is now an endemic disease. With the emergence of new viral variants, COVID-19 is a continuing threat to public health despite the wide availability of vaccines. The virus-encoded trimeric spike protein (S protein) mediates SARS-CoV-2 entry into host cells and also induces strong immune responses, making it an important target for development of therapeutics and vaccines. In this Review, we summarize our latest understanding of the structure and function of the SARS-CoV-2 S protein, the molecular mechanism of viral entry and the emergence of new variants, and we discuss their implications for development of S protein-related intervention strategies.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

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