Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works..
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo-electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:369 |
|---|---|
| Enthalten in: |
Science (New York, N.Y.) - 369(2020), 6510 vom: 18. Sept., Seite 1505-1509 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lv, Zhe [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 21.10.2020 Date Revised 07.12.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1126/science.abc5881 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM31279908X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM31279908X | ||
| 003 | DE-627 | ||
| 005 | 20231225145206.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1126/science.abc5881 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1042.xml |
| 035 | |a (DE-627)NLM31279908X | ||
| 035 | |a (NLM)32703908 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lv, Zhe |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 21.10.2020 | ||
| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. | ||
| 520 | |a The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo-electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Immunoglobulin Fab Fragments |2 NLM | |
| 650 | 7 | |a Receptors, Virus |2 NLM | |
| 650 | 7 | |a Peptidyl-Dipeptidase A |2 NLM | |
| 650 | 7 | |a EC 3.4.15.1 |2 NLM | |
| 650 | 7 | |a ACE2 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 650 | 7 | |a Ace2 protein, mouse |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 650 | 7 | |a Angiotensin-Converting Enzyme 2 |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 700 | 1 | |a Deng, Yong-Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Chun-Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Changfa |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Weijin |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Shihui |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Nie, Jianhui |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Dandan |e verfasserin |4 aut | |
| 700 | 1 | |a Shaw, Neil |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiao-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Qianqian |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Liangzhi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Youchun |e verfasserin |4 aut | |
| 700 | 1 | |a Rao, Zihe |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Cheng-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiangxi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Science (New York, N.Y.) |d 1880 |g 369(2020), 6510 vom: 18. Sept., Seite 1505-1509 |w (DE-627)NLM000023450 |x 1095-9203 |7 nnns |
| 773 | 1 | 8 | |g volume:369 |g year:2020 |g number:6510 |g day:18 |g month:09 |g pages:1505-1509 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1126/science.abc5881 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 369 |j 2020 |e 6510 |b 18 |c 09 |h 1505-1509 | ||