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ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies.
Low, Jun Siong; Jerak, Josipa; Tortorici, M Alejandra; McCallum, Matthew; Pinto, Dora; Cassotta, Antonino; Foglierini, Mathilde; Mele, Federico; Abdelnabi, Rana; Weynand, Birgit; Noack, Julia; Montiel-Ruiz, Martin; Bianchi, Siro; Benigni, Fabio; Sprugasci, Nicole; Joshi, Anshu; Bowen, John E; Stewart, Cameron; Rexhepaj, Megi; Walls, Alexandra C; Jarrossay, David; Morone, Diego; Paparoditis, Philipp; Garzoni, Christian; Ferrari, Paolo; Ceschi, Alessandro; Neyts, Johan; Purcell, Lisa A; Snell, Gyorgy; Corti, Davide; Lanzavecchia, Antonio; Veesler, David; Sallusto, Federica.
  • Low JS; Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
  • Jerak J; Institute of Microbiology, ETH Zürich, 8093 Zurich, Switzerland.
  • Tortorici MA; Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
  • McCallum M; Institute of Microbiology, ETH Zürich, 8093 Zurich, Switzerland.
  • Pinto D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Cassotta A; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Foglierini M; Humabs BioMed SA (subsidiary of Vir Biotechnology), 6500 Bellinzona, Switzerland.
  • Mele F; Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
  • Abdelnabi R; Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
  • Weynand B; Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
  • Noack J; KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium.
  • Montiel-Ruiz M; KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research, B-3000 Leuven, Belgium.
  • Bianchi S; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Benigni F; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Sprugasci N; Humabs BioMed SA (subsidiary of Vir Biotechnology), 6500 Bellinzona, Switzerland.
  • Joshi A; Humabs BioMed SA (subsidiary of Vir Biotechnology), 6500 Bellinzona, Switzerland.
  • Bowen JE; Humabs BioMed SA (subsidiary of Vir Biotechnology), 6500 Bellinzona, Switzerland.
  • Stewart C; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Rexhepaj M; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Walls AC; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Jarrossay D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Morone D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Paparoditis P; Howard Hughes Medical Institute, Seattle, WA 98195, USA.
  • Garzoni C; Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
  • Ferrari P; Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
  • Ceschi A; Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
  • Neyts J; Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese Moncucco, 6900 Lugano, Switzerland.
  • Purcell LA; Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland.
  • Snell G; Department of Internal Medicine, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland.
  • Corti D; Prince of Wales Hospital Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • Lanzavecchia A; Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland.
  • Veesler D; Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland.
  • Sallusto F; Clinical Trial Unit, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland.
Science ; 377(6607): 735-742, 2022 08 12.
Article in English | MEDLINE | ID: covidwho-1949931
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / Broadly Neutralizing Antibodies / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 / Antibodies, Monoclonal / Antibodies, Viral Type of study: Randomized controlled trials Topics: Variants Limits: Animals / Humans Language: English Journal: Science Year: 2022 Document Type: Article Affiliation country: Science.abq2679

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / Broadly Neutralizing Antibodies / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 / Antibodies, Monoclonal / Antibodies, Viral Type of study: Randomized controlled trials Topics: Variants Limits: Animals / Humans Language: English Journal: Science Year: 2022 Document Type: Article Affiliation country: Science.abq2679