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Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion

Alexandra Walls 1 Xiaoli Xiong 1 Young-Jun Park 1 M Alejandra Tortorici 2, 1 Joost Snijder 1 Joel Quispe 1 Elisabetta Cameroni 3 Robin Gopal 4 Mian Dai 5 Antonio Lanzavecchia 6 Maria Zambon 5 Felix Rey 2 Davide Corti 3 David Veesler 1, *
* Corresponding author
1 Department of Biochemistry [Washington ]
2 Virologie Structurale - Structural Virology
3 Humabs BioMed SA
4 Public Health England [London]
5 The Francis Crick Institute [London]
6 Scuola Universitaria Professionale della Svizzera italiana
Abstract : 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.
Keywords : spike glycoprotein neutralizing antibodies membrane fusion glycoproteomics coronavirus class I fusion protein SARS-CoV N-linked glycosylation MERS-CoV
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02546514
Contributor : Maria-Alejandra Tortorici <>
Submitted on : Saturday, April 18, 2020 - 3:37:26 AM
Last modification on : Thursday, February 25, 2021 - 2:32:21 PM

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Alexandra Walls, Xiaoli Xiong, Young-Jun Park, M Alejandra Tortorici, Joost Snijder, et al.. Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion. Cell, Elsevier, 2019, 176 (5), pp.1026-1039.e15. ⟨10.1016/j.cell.2018.12.028⟩. ⟨pasteur-02546514⟩

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