Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved..
There are as yet no licensed therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2, initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralizing SARS-CoV-2, and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilizing CR3022 epitope is inaccessible in the prefusion spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. Cryogenic electron microscopy (cryo-EM) analysis confirms that incubation of spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope could be useful therapeutically, possibly in synergy with an antibody that blocks receptor attachment.
| Errataetall: |
ErratumIn: Cell Host Microbe. 2020 Sep 9;28(3):497. - PMID 32910920 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Cell host & microbe - 28(2020), 3 vom: 09. Sept., Seite 445-454.e6 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huo, Jiandong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.09.2020 Date Revised 20.03.2024 published: Print-Electronic ErratumIn: Cell Host Microbe. 2020 Sep 9;28(3):497. - PMID 32910920 Citation Status MEDLINE |
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| doi: |
10.1016/j.chom.2020.06.010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM311634664 |
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| 245 | 1 | 0 | |a Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike |
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| 500 | |a Date Completed 21.09.2020 | ||
| 500 | |a Date Revised 20.03.2024 | ||
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| 500 | |a ErratumIn: Cell Host Microbe. 2020 Sep 9;28(3):497. - PMID 32910920 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a There are as yet no licensed therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2, initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralizing SARS-CoV-2, and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilizing CR3022 epitope is inaccessible in the prefusion spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. Cryogenic electron microscopy (cryo-EM) analysis confirms that incubation of spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope could be useful therapeutically, possibly in synergy with an antibody that blocks receptor attachment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CR3022 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a X-ray crystallography | |
| 650 | 4 | |a antibody | |
| 650 | 4 | |a cryo-electron microscopy | |
| 650 | 4 | |a epitope | |
| 650 | 4 | |a neutralization | |
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| 700 | 1 | |a Zhao, Yuguang |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Jingshan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Daming |e verfasserin |4 aut | |
| 700 | 1 | |a Duyvesteyn, Helen M E |e verfasserin |4 aut | |
| 700 | 1 | |a Ginn, Helen M |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 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 Coombes, Naomi |e verfasserin |4 aut | |
| 700 | 1 | |a Bewley, Kevin R |e verfasserin |4 aut | |
| 700 | 1 | |a Tree, Julia A |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, 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 |e verfasserin |4 aut | |
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| 700 | 1 | |a Owens, Raymond J |e verfasserin |4 aut | |
| 700 | 1 | |a Stuart, David I |e verfasserin |4 aut | |
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