Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
The COVID-19 pandemic has had an unprecedented health and economic impact and there are currently no approved therapies. We have isolated an antibody, EY6A, from an individual convalescing from COVID-19 and have shown that it neutralizes SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds the receptor binding domain (RBD) of the viral spike glycoprotein tightly (KD of 2 nM), and a 2.6-Å-resolution crystal structure of an RBD-EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues within this footprint are key to stabilizing the pre-fusion spike. Cryo-EM analyses of the pre-fusion spike incubated with EY6A Fab reveal a complex of the intact spike trimer with three Fabs bound and two further multimeric forms comprising the destabilized spike attached to Fab. EY6A binds what is probably a major neutralizing epitope, making it a candidate therapeutic for COVID-19.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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Enthalten in: |
Nature structural & molecular biology - 27(2020), 10 vom: 14. Okt., Seite 950-958 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Zhou, Daming [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 29.10.2020 Date Revised 20.03.2024 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1038/s41594-020-0480-y |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM313129428 |
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520 | |a The COVID-19 pandemic has had an unprecedented health and economic impact and there are currently no approved therapies. We have isolated an antibody, EY6A, from an individual convalescing from COVID-19 and have shown that it neutralizes SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds the receptor binding domain (RBD) of the viral spike glycoprotein tightly (KD of 2 nM), and a 2.6-Å-resolution crystal structure of an RBD-EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues within this footprint are key to stabilizing the pre-fusion spike. Cryo-EM analyses of the pre-fusion spike incubated with EY6A Fab reveal a complex of the intact spike trimer with three Fabs bound and two further multimeric forms comprising the destabilized spike attached to Fab. EY6A binds what is probably a major neutralizing epitope, making it a candidate therapeutic for COVID-19 | ||
650 | 4 | |a Journal Article | |
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650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
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700 | 1 | |a Duyvesteyn, Helen M E |e verfasserin |4 aut | |
700 | 1 | |a Chen, Cheng-Pin |e verfasserin |4 aut | |
700 | 1 | |a Huang, Chung-Guei |e verfasserin |4 aut | |
700 | 1 | |a Chen, Ting-Hua |e verfasserin |4 aut | |
700 | 1 | |a Shih, Shin-Ru |e verfasserin |4 aut | |
700 | 1 | |a Lin, Yi-Chun |e verfasserin |4 aut | |
700 | 1 | |a Cheng, Chien-Yu |e verfasserin |4 aut | |
700 | 1 | |a Cheng, Shu-Hsing |e verfasserin |4 aut | |
700 | 1 | |a Huang, Yhu-Chering |e verfasserin |4 aut | |
700 | 1 | |a Lin, Tzou-Yien |e verfasserin |4 aut | |
700 | 1 | |a Ma, Che |e verfasserin |4 aut | |
700 | 1 | |a Huo, Jiandong |e verfasserin |4 aut | |
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700 | 1 | |a Malinauskas, Tomas |e verfasserin |4 aut | |
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700 | 1 | |a Shah, Pranav N M |e verfasserin |4 aut | |
700 | 1 | |a Tan, Tiong Kit |e verfasserin |4 aut | |
700 | 1 | |a Rijal, Pramila |e verfasserin |4 aut | |
700 | 1 | |a Donat, Robert F |e verfasserin |4 aut | |
700 | 1 | |a Godwin, Kerry |e verfasserin |4 aut | |
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700 | 1 | |a Radecke, Julika |e verfasserin |4 aut | |
700 | 1 | |a Paterson, Neil G |e verfasserin |4 aut | |
700 | 1 | |a Supasa, Piyada |e verfasserin |4 aut | |
700 | 1 | |a Mongkolsapaya, Juthathip |e verfasserin |4 aut | |
700 | 1 | |a Screaton, Gavin R |e verfasserin |4 aut | |
700 | 1 | |a Carroll, Miles W |e verfasserin |4 aut | |
700 | 1 | |a Gilbert-Jaramillo, Javier |e verfasserin |4 aut | |
700 | 1 | |a Knight, Michael L |e verfasserin |4 aut | |
700 | 1 | |a James, William |e verfasserin |4 aut | |
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700 | 1 | |a Ren, Jingshan |e verfasserin |4 aut | |
700 | 1 | |a Stuart, David I |e verfasserin |4 aut | |
700 | 1 | |a Huang, Kuan-Ying A |e verfasserin |4 aut | |
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