ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies
| Autor: | Jun Siong Low, Josipa Jerak, M. Alejandra Tortorici, Matthew McCallum, Dora Pinto, Antonino Cassotta, Mathilde Foglierini, Federico Mele, Rana Abdelnabi, Birgit Weynand, Julia Noack, Martin Montiel-Ruiz, Siro Bianchi, Fabio Benigni, Nicole Sprugasci, Anshu Joshi, John E. Bowen, Cameron Stewart, Megi Rexhepaj, Alexandra C. Walls, David Jarrossay, Diego Morone, Philipp Paparoditis, Christian Garzoni, Paolo Ferrari, Alessandro Ceschi, Johan Neyts, Lisa A. Purcell, Gyorgy Snell, Davide Corti, Antonio Lanzavecchia, David Veesler, Federica Sallusto |
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| Přispěvatelé: | University of Zurich, Low, Jun Siong, Veesler, David, Sallusto, Federica |
| Rok vydání: | 2022 |
| Předmět: |
1000 Multidisciplinary
Multidisciplinary SARS-CoV-2 Antibodies Monoclonal COVID-19 610 Medicine & health Antibodies Viral Antibodies Neutralizing 10199 Clinic for Clinical Pharmacology and Toxicology Spike Glycoprotein Coronavirus Animals Humans Angiotensin-Converting Enzyme 2 Peptides Broadly Neutralizing Antibodies Protein Binding |
| Zdroj: | Science. 377:735-742 |
| ISSN: | 1095-9203 0036-8075 |
| Popis: | 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. ispartof: SCIENCE vol:377 issue:6607 pages:735-741 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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