Open Access

Science, volume 371, issue 6530

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

Paul-Albert Koenig ^{1, 2}

Hrishikesh Das ³

Hejun Liu ⁴

Beate M Kümmerer ^{5, 6}

Florian N Gohr ²

Lea Marie Jenster ²

Lisa Dj Schiffelers ²

Yonas M Tesfamariam ²

Miki Uchima ²

Jennifer Deborah Wuerth ²

Karl Gatterdam ⁷

Natalia Ruétalo ⁸

Maria H. Christensen ²

Caroline I Fandrey ²

Sabine Normann ²

Jan Mp Tödtmann ¹

Steffen Pritzl ¹

Leo Hanke ⁹

Jannik Boos ¹⁰

Meng Yuan ⁴

Xue-Yong Zhu ⁴

J. Schmid-Burgk ¹¹

Hiroki Kato ¹²

Michael Schindler ⁸

I. H. Wilson ^{4, 13}

Matthias Geyer ⁷

Kerstin U. Ludwig ¹⁰

B. Martin Hallberg ^{3, 14}

Nicholas Wu ^{15, 16, 17}

Florian I. Schmidt ^{1, 2}

Hide authors affiliations Show authors affiliations: 17 affiliations

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

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

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. |

Publication type: Journal Article

Publication date: 2021-02-12

American Association for the Advancement of Science (AAAS)

Journal: Science

SJR: 11.902

CiteScore: 61.1

Impact factor: 44.7

ISSN: 00368075, 10959203

DOI: 10.1126/science.abe6230

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Multidisciplinary

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

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Koenig P. et al. Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape // Science. 2021. Vol. 371. No. 6530.

GOST all authors (up to 50) Copy

Koenig P., Das H., Liu H., Kümmerer B. M., Gohr F. N., Jenster L. M., Schiffelers L. D., Tesfamariam Y. M., Uchima M., Wuerth J. D., Gatterdam K., Ruétalo N., Christensen M. H., Fandrey C. I., Normann S., Tödtmann J. M., Pritzl S., Hanke L., Boos J., Yuan M., Zhu X., Schmid-Burgk J., Kato H., Schindler M., Wilson I. H., Geyer M., Ludwig K. U., Hallberg B. M., Wu N., Schmidt F. I. Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape // Science. 2021. Vol. 371. No. 6530.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1126/science.abe6230

UR - https://doi.org/10.1126/science.abe6230

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

T2 - Science

AU - Koenig, Paul-Albert

AU - Das, Hrishikesh

AU - Liu, Hejun

AU - Kümmerer, Beate M

AU - Gohr, Florian N

AU - Jenster, Lea Marie

AU - Schiffelers, Lisa Dj

AU - Tesfamariam, Yonas M

AU - Uchima, Miki

AU - Wuerth, Jennifer Deborah

AU - Gatterdam, Karl

AU - Ruétalo, Natalia

AU - Christensen, Maria H.

AU - Fandrey, Caroline I

AU - Normann, Sabine

AU - Tödtmann, Jan Mp

AU - Pritzl, Steffen

AU - Hanke, Leo

AU - Boos, Jannik

AU - Yuan, Meng

AU - Zhu, Xue-Yong

AU - Schmid-Burgk, J.

AU - Kato, Hiroki

AU - Schindler, Michael

AU - Wilson, I. H.

AU - Geyer, Matthias

AU - Ludwig, Kerstin U.

AU - Hallberg, B. Martin

AU - Wu, Nicholas

AU - Schmidt, Florian I.

PY - 2021

DA - 2021/02/12

PB - American Association for the Advancement of Science (AAAS)

IS - 6530

VL - 371

SN - 0036-8075

SN - 1095-9203

ER -

BibTex

Cite this

BibTex (up to 50 authors) Copy

@article{2021_Koenig,

author = {Paul-Albert Koenig and Hrishikesh Das and Hejun Liu and Beate M Kümmerer and Florian N Gohr and Lea Marie Jenster and Lisa Dj Schiffelers and Yonas M Tesfamariam and Miki Uchima and Jennifer Deborah Wuerth and Karl Gatterdam and Natalia Ruétalo and Maria H. Christensen and Caroline I Fandrey and Sabine Normann and Jan Mp Tödtmann and Steffen Pritzl and Leo Hanke and Jannik Boos and Meng Yuan and Xue-Yong Zhu and J. Schmid-Burgk and Hiroki Kato and Michael Schindler and I. H. Wilson and Matthias Geyer and Kerstin U. Ludwig and B. Martin Hallberg and Nicholas Wu and Florian I. Schmidt},

title = {Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape},

journal = {Science},

year = {2021},

volume = {371},

publisher = {American Association for the Advancement of Science (AAAS)},

month = {feb},

url = {https://doi.org/10.1126/science.abe6230},

number = {6530},

doi = {10.1126/science.abe6230}

}

Found error?

Publisher

American Association for the Advancement of Science (AAAS)

Journal

Science

SJR

11.902

CiteScore

61.1

Impact factor

44.7

ISSN

00368075 (Print)

10959203 (Electronic)