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Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies.
Wrapp, Daniel; De Vlieger, Dorien; Corbett, Kizzmekia S; Torres, Gretel M; Wang, Nianshuang; Van Breedam, Wander; Roose, Kenny; van Schie, Loes; Hoffmann, Markus; Pöhlmann, Stefan; Graham, Barney S; Callewaert, Nico; Schepens, Bert; Saelens, Xavier; McLellan, Jason S.
  • Wrapp D; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • De Vlieger D; VIB-UGent Center for Medical Biotechnology, VIB, 9052 Ghent, Belgium; Department of Biochemistry and Microbiology, Ghent University, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
  • Corbett KS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Torres GM; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
  • Wang N; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Van Breedam W; VIB-UGent Center for Medical Biotechnology, VIB, 9052 Ghent, Belgium; Department of Biochemistry and Microbiology, Ghent University, 9052 Ghent, Belgium.
  • Roose K; VIB-UGent Center for Medical Biotechnology, VIB, 9052 Ghent, Belgium; Department of Biochemistry and Microbiology, Ghent University, 9052 Ghent, Belgium.
  • van Schie L; VIB-UGent Center for Medical Biotechnology, VIB, 9052 Ghent, Belgium; Department of Biochemistry and Microbiology, Ghent University, 9052 Ghent, Belgium.
  • Hoffmann M; Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, 37077 Göttingen, Germany.
  • Pöhlmann S; Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, 37077 Göttingen, Germany; Faculty of Biology and Psychology, University Göttingen, 37077 Göttingen, Germany.
  • Graham BS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Callewaert N; VIB-UGent Center for Medical Biotechnology, VIB, 9052 Ghent, Belgium; Department of Biochemistry and Microbiology, Ghent University, 9052 Ghent, Belgium.
  • Schepens B; VIB-UGent Center for Medical Biotechnology, VIB, 9052 Ghent, Belgium; Department of Biochemistry and Microbiology, Ghent University, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium. Electronic address: bert.schepens@vib-ugent.be.
  • Saelens X; VIB-UGent Center for Medical Biotechnology, VIB, 9052 Ghent, Belgium; Department of Biochemistry and Microbiology, Ghent University, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium. Electronic address: xavier.saelens@vib-ugent.be.
  • McLellan JS; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: jmclellan@austin.utexas.edu.
Cell ; 181(5): 1004-1015.e15, 2020 05 28.
Article in English | MEDLINE | ID: covidwho-88549
ABSTRACT
Coronaviruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics. Here, we describe the isolation of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs neutralize MERS-CoV or SARS-CoV-1 S pseudotyped viruses, respectively. Crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs interfere with receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S and demonstrate that this cross-reactive VHH neutralizes SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Single-Domain Antibodies / Betacoronavirus Type of study: Randomized controlled trials Limits: Animals Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.04.031

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Single-Domain Antibodies / Betacoronavirus Type of study: Randomized controlled trials Limits: Animals Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.04.031