ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies-Reference-Cited by-同舟云学术

ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies

Published:2022-08-12 Issue:6607 Volume:377 Page:735-742
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Low Jun Siong¹²^ORCID,Jerak Josipa¹²^ORCID,Tortorici M. Alejandra³^ORCID,McCallum Matthew³^ORCID,Pinto Dora⁴,Cassotta Antonino¹^ORCID,Foglierini Mathilde¹^ORCID,Mele Federico¹^ORCID,Abdelnabi Rana⁵^ORCID,Weynand Birgit⁶^ORCID,Noack Julia⁷^ORCID,Montiel-Ruiz Martin⁷^ORCID,Bianchi Siro⁴^ORCID,Benigni Fabio⁴^ORCID,Sprugasci Nicole⁴^ORCID,Joshi Anshu³,Bowen John E.³^ORCID,Stewart Cameron³^ORCID,Rexhepaj Megi³^ORCID,Walls Alexandra C.³⁸^ORCID,Jarrossay David¹^ORCID,Morone Diego¹,Paparoditis Philipp¹,Garzoni Christian⁹^ORCID,Ferrari Paolo¹⁰¹¹¹²^ORCID,Ceschi Alessandro¹⁰¹³¹⁴¹⁵^ORCID,Neyts Johan⁵¹⁶^ORCID,Purcell Lisa A.⁷^ORCID,Snell Gyorgy⁷^ORCID,Corti Davide⁴^ORCID,Lanzavecchia Antonio⁴¹⁷^ORCID,Veesler David³⁸^ORCID,Sallusto Federica¹²^ORCID

Affiliation:

1. Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.

2. Institute of Microbiology, ETH Zürich, 8093 Zurich, Switzerland.

3. Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.

4. Humabs BioMed SA (subsidiary of Vir Biotechnology), 6500 Bellinzona, Switzerland.

5. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium.

6. KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research, B-3000 Leuven, Belgium.

7. Vir Biotechnology, San Francisco, CA 94158, USA.

8. Howard Hughes Medical Institute, Seattle, WA 98195, USA.

9. Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese Moncucco, 6900 Lugano, Switzerland.

10. Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland.

11. Department of Internal Medicine, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland.

12. Prince of Wales Hospital Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.

13. Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland.

14. Clinical Trial Unit, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland.

15. Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, 8091 Zurich, Switzerland.

16. Global Virus Network, Baltimore, MD 21201, USA.

17. National Institute of Molecular Genetics, 20122 Milano, Italy.

Abstract

The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus spike proteins from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide and acquire affinity and breadth through somatic mutations. Despite targeting a conserved motif, only some mAbs show broad neutralizing activity in vitro against alpha- and betacoronaviruses, including animal coronaviruses WIV-1 and PDF-2180. Two selected mAbs also neutralize Omicron BA.1 and BA.2 authentic viruses and reduce viral burden and pathology in vivo. Structural and functional analyses showed that the fusion peptide–specific mAbs bound with different modalities to a cryptic epitope hidden in prefusion stabilized spike, which became exposed upon binding of angiotensin-converting enzyme 2 (ACE2) or ACE2-mimicking mAbs.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference106 articles.

1. Novel Canine Coronavirus Isolated from a Hospitalized Pneumonia Patient, East Malaysia

2. Independent infections of porcine deltacoronavirus among Haitian children

3. Structure, receptor recognition, and antigenicity of the human coronavirus CCoV-HuPn-2018 spike glycoprotein

4. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

5. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Cited by 109 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Revisiting the dimensions of universal vaccine with special focus on COVID-19: Efficacy versus methods of designing;International Journal of Biological Macromolecules;2024-10

2. Bispecific Antibodies Provide Broad Neutralization of Emerging Beta-Coronaviruses by Targeting ACE2 and Viral Spikes;Emerging Microbes & Infections;2024-09-11

3. Nasopharyngeal specific selection and emergence of SARS-CoV-2 spike fusion peptide mutation P812S during chronic infection;2024-09-06

4. Aging and viral evolution impair immunity against dominant pan-coronavirus-reactive T cell epitope;2024-08-21

5. The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2;PLOS Pathogens;2024-08-02