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Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion
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Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses. The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies. To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors. Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry. These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.
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“Protection is thought to be mediated by neutralizing antibodies against the S protein (7, 8)”
From An Alphavirus -derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates (2020) · cites this paper as [7]
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Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S., & McLellan, J. S. (2020) · Science · doi:10.1126/science.abb2507 · Cited by 8,897
Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein
Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020) · doi:10.1101/2020.02.19.956581 · Cited by 8,586
Self-citationStructure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor
Lan, J., Ge, J., Yu, J., Shan, S., Zhou, H., Fan, S., Zhang, Q., Shi, X., Wang, Q., Zhang, L., et al. (2020) · Nature · doi:10.1038/s41586-020-2180-5 · Cited by 5,983
Starr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.012 · Cited by 1,956
Self-citationCross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody
Pinto, D., Park, Y.-J., Beltramello, M., Walls, A. C., Tortorici, M. A., Bianchi, S., Jaconi, S., Culap, K., Zatta, F., De Marco, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2349-y · Cited by 1,885
Self-citation
Metadata
- Authors
- Walls, A. C., Xiong, X., Park, Y.-J., Tortorici, M. A., Snijder, J., Quispe, J., Cameroni, E., Gopal, R., Dai, M., Lanzavecchia, A., Zambon, M., Rey, F. A., Corti, D., & Veesler, D.
- Affiliations
- University of Washington (US)
- Centre National de la Recherche Scientifique (FR)
- Vir Biotechnology (Switzerland) (CH)
- Public Health England (GB)
- The Francis Crick Institute (GB)
- Institute for Research in Biomedicine (CH)
- Corresponding author
- Veesler, David
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 176
- Issue
- 5
- Pages
- 1026-1039.e15
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6751136
- OpenAlex
- W2915009278
- Cited by
- 582
- References
- 85
- Citations by year
- 2026: 7 · 2025: 25 · 2024: 30 · 2023: 40 · 2022: 79 · 2021: 173 · 2020: 214 · 2019: 14
- FWCI
- 92.33
- Type
- journal article
- Language
- en
- Update notices
- erratum (2020-12-10)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- National Institute of General Medical Sciences (R01GM120553)
- National Institute of Allergy and Infectious Diseases (HHSN272201700059C)
- Pew Biomedical Scholars Award
- Burroughs Wellcome Fund
- Netherlands Organisation for Scientific Research (Rubicon 019.2015.2.310.006)
- European Molecular Biology Organization (ALTF933-2015)
- Zoonoses Anticipation and Preparedness Initiative (IMI115760)
- Pasteur Institute
- Centre National de la Recherche Scientifique
- LabEx Integrative Biology of Emerging Infectious Diseases
- University of Washington Arnold and Mabel Beckman CryoEM Center and Proteomics Resource (UWPR95794)
- Advanced Light Source at Lawrence Berkley National Laboratory
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV, MERS-CoV, neutralizing antibodies, antibody-antigen complex structure, humoral immune response, viral entry, receptor binding
- MeSH terms
- Animals, Antibodies, Monoclonal, Antibodies, Viral, Chlorocebus aethiops, Humans, Protein Binding, Receptors, Virus, Vero Cells, Coronavirus, Coronavirus Infections, Molecular Mimicry, Severe acute respiratory syndrome-related coronavirus, Virus Internalization, Immunity, Humoral, Antibodies, Neutralizing, HEK293 Cells, Spike Glycoprotein, Coronavirus, Middle East Respiratory Syndrome Coronavirus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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