Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape-Reference-Cited by-同舟云学术

Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape

Published:2021-02-12 Issue:6530 Volume:371 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Koenig Paul-Albert¹²^ORCID,Das Hrishikesh³^ORCID,Liu Hejun⁴^ORCID,Kümmerer Beate M.⁵⁶,Gohr Florian N.²^ORCID,Jenster Lea-Marie²^ORCID,Schiffelers Lisa D. J.²^ORCID,Tesfamariam Yonas M.²^ORCID,Uchima Miki²^ORCID,Wuerth Jennifer D.²^ORCID,Gatterdam Karl⁷^ORCID,Ruetalo Natalia⁸,Christensen Maria H.²^ORCID,Fandrey Caroline I.²^ORCID,Normann Sabine²,Tödtmann Jan M. P.¹^ORCID,Pritzl Steffen¹,Hanke Leo⁹^ORCID,Boos Jannik¹⁰^ORCID,Yuan Meng⁴^ORCID,Zhu Xueyong⁴^ORCID,Schmid-Burgk Jonathan L.¹¹^ORCID,Kato Hiroki¹²,Schindler Michael⁸^ORCID,Wilson Ian A.⁴¹³^ORCID,Geyer Matthias⁷^ORCID,Ludwig Kerstin U.¹⁰^ORCID,Hällberg B. Martin³¹⁴^ORCID,Wu Nicholas C.¹⁵¹⁶¹⁷^ORCID,Schmidt Florian I.¹²^ORCID

Affiliation:

1. Core Facility Nanobodies, Medical Faculty, University of Bonn, 53127 Bonn, Germany.

2. Institute of Innate Immunity, Medical Faculty, University of Bonn, 53127 Bonn, Germany.

3. Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden.

4. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

5. Institute of Virology, Medical Faculty, University of Bonn, 53127 Bonn, Germany.

6. German Centre for Infection Research (DZIF), partner site Bonn-Cologne, 53127 Bonn, Germany.

7. Institute of Structural Biology, Medical Faculty, University of Bonn, 53127 Bonn, Germany.

8. Institute for Medical Virology and Epidemiology, Section Molecular Virology, University Hospital Tübingen, 72076 Tübingen, Germany.

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

10. Institute of Human Genetics, Medical Faculty, University of Bonn, 53127 Bonn, Germany.

11. Institute for Clinical Chemistry and Clinical Pharmacology, Medical Faculty, University of Bonn, 53127 Bonn, Germany.

12. Institute of Cardiovascular Immunology, Medical Faculty, University of Bonn, 53127 Bonn, Germany.

13. The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

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

15. Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

16. Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

17. Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Abstract

A double punch against SARS-CoV-2 Monoclonal antibodies are an important weapon in the battle against COVID-19. However, these large proteins are difficult to produce in the needed quantities and at low cost. Attention has turned to nanobodies, which are aptly named, single-domain antibodies that are easier to produce and have the potential to be administered by inhalation. Koenig et al. describe four nanobodies that bind to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and prevent infection of cells (see the Perspective by Saelens and Schepens). Structures show that the nanobodies target two distinct epitopes on the SARS-CoV-2 spike protein. Multivalent nanobodies neutralize virus much more potently than single nanobodies, and multivalent nanobodies that bind two epitopes prevent the emergence of viral escape mutants. Science , this issue p. eabe6230 ; see also p. 681

Funder

Bill and Melinda Gates Foundation

University of Illinois at Urbana-Champaign

Baden-Württemberg Stiftung

Horizon 2020 Framework Programme

Universitätsklinikum Tübingen

Deutsche Forschungsgemeinschaft

Knut och Alice Wallenbergs Stiftelse

Vetenskapsrådet

Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg

Klaus Tschira Stiftung

Bundesministerium für Bildung und Forschung