Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
Abstract The COVID-19 pandemic has had unprecedented health and economic impact, but currently there are no approved therapies. We have isolated an antibody, EY6A, from a late-stage COVID-19 patient and show it neutralises SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds tightly (KD of 2 nM) the receptor binding domain (RBD) of the viral Spike glycoprotein and a 2.6Å crystal structure of an RBD/EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues of this epitope are key to stabilising the pre-fusion Spike. Cryo-EM analyses of the pre-fusion Spike incubated with EY6A Fab reveal a complex of the intact trimer with three Fabs bound and two further multimeric forms comprising destabilized Spike attached to Fab. EY6A binds what is probably a major neutralising epitope, making it a candidate therapeutic for COVID-19..
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Preprint| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
bioRxiv.org - (2020) vom: 08. Dez. Zur Gesamtaufnahme - year:2020 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Daming [VerfasserIn] |
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| Links: |
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| doi: |
10.1101/2020.06.12.148387 |
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| PPN (Katalog-ID): |
XBI018127924 |
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| 245 | 1 | 0 | |a Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient |
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| 520 | |a Abstract The COVID-19 pandemic has had unprecedented health and economic impact, but currently there are no approved therapies. We have isolated an antibody, EY6A, from a late-stage COVID-19 patient and show it neutralises SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds tightly (KD of 2 nM) the receptor binding domain (RBD) of the viral Spike glycoprotein and a 2.6Å crystal structure of an RBD/EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues of this epitope are key to stabilising the pre-fusion Spike. Cryo-EM analyses of the pre-fusion Spike incubated with EY6A Fab reveal a complex of the intact trimer with three Fabs bound and two further multimeric forms comprising destabilized Spike attached to Fab. EY6A binds what is probably a major neutralising epitope, making it a candidate therapeutic for COVID-19. | ||
| 700 | 1 | |a Duyvesteyn, Helen ME |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 | |
| 700 | 1 | |a Carrique, Loic |e verfasserin |4 aut | |
| 700 | 1 | |a Malinauskas, Tomas |e verfasserin |4 aut | |
| 700 | 1 | |a Ruza, Reinis R |e verfasserin |4 aut | |
| 700 | 1 | |a Shah, Pranav NM |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 | |
| 700 | 1 | |a Buttigieg, Karen |e verfasserin |4 aut | |
| 700 | 1 | |a Tree, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Radecke, Julika |e verfasserin |4 aut | |
| 700 | 1 | |a Paterson, Neil G |e verfasserin |4 aut | |
| 700 | 1 | |a Supasa, Piyasa |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 Jaramillo, Javier G. |e verfasserin |4 aut | |
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| 700 | 1 | |a Owens, Raymond J |e verfasserin |4 aut | |
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| 700 | 1 | |a Townsend, Alain |e verfasserin |4 aut | |
| 700 | 1 | |a Fry, Elizabeth E |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yuguang |e verfasserin |4 aut | |
| 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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