PreprintCited by 365SARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approachesAnimal Virus Infections Studies

Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants

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Yuan, Meng, Huang, Deli, Lee, Chang-Chun D., Wu, Nicholas C., Jackson, Abigail M., Zhu, Xueyong, Liu, Hejun, Peng, Linghang +9 more·2021·Science

Abstract

The protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the recent SARS-CoV-2 variants. Residues E484 and K417 in the receptor-binding site (RBS) are both mutated in lineages first described in South Africa (B.1.351) and Brazil (B.1.1.28.1). The nAbs isolated from SARS-CoV-2 patients are preferentially encoded by certain heavy-chain germline genes and the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2) can each bind the RBS in two different binding modes. However, their binding and neutralization are abrogated by either the E484K or K417N mutation, whereas nAbs to the cross-reactive CR3022 and S309 sites are largely unaffected. This structural and functional analysis illustrates why mutations at E484 and K417 adversely affect major classes of nAbs to SARS-CoV-2 with consequences for next-generation COVID-19 vaccines.

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Crossref · 10.1101/2021.02.16.430500

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  • The B.1.351 and P.1 SARS-CoV-2 variants carry a glutamate-to-lysine mutation at position 484 (E484K) in the spike protein receptor-binding domain, which promotes immune evasion.

    “The B.1.351 and P.1 variants have a glutamate (E) to lysine (K) mutation at position 484 (E484K) in the receptor-binding domain of the spike protein, which promotes immune evasion207.”

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Authors
Yuan, M., Huang, D., Lee, C.-C. D., Wu, N. C., Jackson, A. M., Zhu, X., Liu, H., Peng, L., van Gils, M. J., Sanders, R. W., Burton, D. R., Reincke, S. M., Prüss, H., Kreye, J., Nemazee, D., Ward, A. B., & Wilson, I. A.
Affiliations
  • Scripps Research Institute (US)
  • University of Illinois Urbana-Champaign (US)
  • Cornell University (US)
  • German Center for Neurodegenerative Diseases (DE)
Corresponding author
Wilson, Ian A.
Venue
Science
Publisher
openRxiv
Published
2021-02-17
Volume
373
Issue
6556
Pages
818-823
ISSN
0036-8075 (ISSN-L)
OpenAlex
W3160471157
Cited by
364
References
112
Citations by year
2026: 11 · 2025: 27 · 2024: 35 · 2023: 60 · 2022: 138 · 2021: 92 · 2020: 1
FWCI
25.73
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by-nc)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • DZNE Pub (submittedVersion)
Funders
  • U.S. Department of Energy (DE‐ AC02‐06CH11357, COVID-19, Contract No. DE-AC02-06CH11357., AC02‐06CH11357, 06CH11357, No. DE-AC02-06CH11357, DE-AC02-)
  • Bill and Melinda Gates Foundation (INV-004923, OPP1170236, OPP1170236 and INV-004923)
  • Helmholtz-Gemeinschaft (HIL-A03 and SO-097)
  • Deutsche Forschungsgemeinschaft (PR1274/5–1, and PR 1274/5-1, DE-AC02-06CH11357, PR1274/3–1, PR 1274/3-1, and PR 1274/5-1)
  • Bundesministerium für Bildung und Forschung (01GM1908D)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek
  • National Institutes of Health (COVID-19, DE-AC02–06CH11357, AI110657)
  • Office of Science (Contract No. DE-AC02-06CH11357, AC02‐06CH11357, DE-AC02, No. DE-AC02-06CH11357., 06CH11357, DE-AC02-06CH11357)
  • National Institute of Allergy and Infectious Diseases (R01AI142945, R01AI132317, P01AI110657, R00AI139445)
  • Argonne National Laboratory (DE- AC02-06-CH11357, DE-AC02, AC02–06CH11357, No. DE-AC02-06CH11357, 06CH11357, Contract No. DE-AC02-06CH11357.)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Keywords
SARS-CoV-2, antigenic drift, Beta variant, P.1, spike protein mutations, K417N, E484K, receptor binding sites, ACE2 binding, neutralizing antibodies, CR3022, vaccine design, antibody therapy

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