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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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Prefusion spike protein stabilization through computational mutagenesis
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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
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