Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
04 11 2020
Historique:
received: 16 06 2020
accepted: 01 10 2020
entrez: 5 11 2020
pubmed: 6 11 2020
medline: 18 11 2020
Statut: epublish

Résumé

The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Therapeutic neutralizing antibodies constitute a key short-to-medium term approach to tackle COVID-19. However, traditional antibody production is hampered by long development times and costly production. Here, we report the rapid isolation and characterization of nanobodies from a synthetic library, known as sybodies (Sb), that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Several binders with low nanomolar affinities and efficient neutralization activity were identified of which Sb23 displayed high affinity and neutralized pseudovirus with an IC

Identifiants

pubmed: 33149112
doi: 10.1038/s41467-020-19204-y
pii: 10.1038/s41467-020-19204-y
pmc: PMC7642358
doi:

Substances chimiques

Antibodies, Monoclonal 0
Antibodies, Neutralizing 0
Antibodies, Viral 0
Receptors, Virus 0
Single-Domain Antibodies 0
Spike Glycoprotein, Coronavirus 0
spike protein, SARS-CoV-2 0
Peptidyl-Dipeptidase A EC 3.4.15.1
ACE2 protein, human EC 3.4.17.23
Angiotensin-Converting Enzyme 2 EC 3.4.17.23

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5588

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Auteurs

Tânia F Custódio (TF)

Centre for Structural Systems Biology (CSSB), DESY and European Molecular Biology Laboratory Hamburg, Notkestrasse 85, D-22607, Hamburg, Germany.

Hrishikesh Das (H)

Centre for Structural Systems Biology (CSSB) and Karolinska Institutet VR-RÅC, Notkestrasse 85, D-22607, Hamburg, Germany.

Daniel J Sheward (DJ)

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, 17177, Sweden.
Division of Virology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

Leo Hanke (L)

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, 17177, Sweden.

Samuel Pazicky (S)

Centre for Structural Systems Biology (CSSB), DESY and European Molecular Biology Laboratory Hamburg, Notkestrasse 85, D-22607, Hamburg, Germany.

Joanna Pieprzyk (J)

Centre for Structural Systems Biology (CSSB), DESY and European Molecular Biology Laboratory Hamburg, Notkestrasse 85, D-22607, Hamburg, Germany.

Michèle Sorgenfrei (M)

Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.

Martin A Schroer (MA)

European Molecular Biology Laboratory (EMBL), Hamburg Outstation c/o Deutsches Elektronen Synchrotron (DESY), Notkestrasse 85, D-22607, Hamburg, Germany.

Andrey Yu Gruzinov (AY)

European Molecular Biology Laboratory (EMBL), Hamburg Outstation c/o Deutsches Elektronen Synchrotron (DESY), Notkestrasse 85, D-22607, Hamburg, Germany.

Cy M Jeffries (CM)

European Molecular Biology Laboratory (EMBL), Hamburg Outstation c/o Deutsches Elektronen Synchrotron (DESY), Notkestrasse 85, D-22607, Hamburg, Germany.

Melissa A Graewert (MA)

European Molecular Biology Laboratory (EMBL), Hamburg Outstation c/o Deutsches Elektronen Synchrotron (DESY), Notkestrasse 85, D-22607, Hamburg, Germany.

Dmitri I Svergun (DI)

European Molecular Biology Laboratory (EMBL), Hamburg Outstation c/o Deutsches Elektronen Synchrotron (DESY), Notkestrasse 85, D-22607, Hamburg, Germany.

Nikolay Dobrev (N)

European Molecular Biology Laboratory (EMBL) Heidelberg, Protein Expression and Purification Core Facility, 69117, Heidelberg, Germany.

Kim Remans (K)

European Molecular Biology Laboratory (EMBL) Heidelberg, Protein Expression and Purification Core Facility, 69117, Heidelberg, Germany.

Markus A Seeger (MA)

Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.

Gerald M McInerney (GM)

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, 17177, Sweden.

Ben Murrell (B)

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, 17177, Sweden. benjamin.murrell@ki.se.

B Martin Hällberg (BM)

Centre for Structural Systems Biology (CSSB) and Karolinska Institutet VR-RÅC, Notkestrasse 85, D-22607, Hamburg, Germany. martin.hallberg@ki.se.
Department of Cell and Molecular Biology, Karolinska Institutet, 17177, Stockholm, Sweden. martin.hallberg@ki.se.

Christian Löw (C)

Centre for Structural Systems Biology (CSSB), DESY and European Molecular Biology Laboratory Hamburg, Notkestrasse 85, D-22607, Hamburg, Germany. christian.loew@embl-hamburg.de.

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Classifications MeSH