Open Access

Science, volume 370, issue 6523, pages 1473-1479

An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike

Michael Schoof ^{1, 2}

Bryan Faust ^{1, 2, 3, 4}

Reuben A Saunders ^{1, 5}

Smriti Sangwan ^{1, 2}

Veronica V Rezelj ⁶

Nick Hoppe ^{3, 4}

Morgane Boone ^{1, 2}

Christian B Billesbølle ^{3, 4}

Cristina Puchades ⁴

C. M. Azumaya ⁴

H. Kratochvil ⁴

Marcell Zimanyi ^{1, 2}

Ishan Deshpande ^{3, 4}

Jiahao Liang ³

Miles Sasha Dickinson ⁴

Kim Cuong Nguyen ⁴

Cynthia M Chio ⁴

Gregory E Merz ⁴

Michael C. Thompson ⁴

Devan Diwanji ⁴

Kaitlin Schaefer ⁴

Aditya A Anand ^{1, 2}

Niv Dobzinski ^{1, 2}

Beth S. Zha ⁷

Camille R. Simoneau ^{8, 9, 10}

Kristoffer E Leon ^{8, 9, 10}

Kris M White ^{11, 12}

Un Seng Chio ⁴

Meghna Gupta ⁴

M Jin ⁴

Fei Li ⁴

Yanxin Liu ⁴

Kaihua Zhang ⁴

David Bulkley ⁴

Ming Sun ⁴

Joel M Smith ⁴

Alexandrea Rizo ⁴

Frank R Moss ⁴

Axel F. Brilot ⁴

Sergei Pourmal ⁴

R Trenker ⁴

Thomas H Pospiech ⁴

Sayan Gupta ¹³

Benjamin Barsi Rhyne ³

Vladislav Belyy ^{1, 2}

Andrew W Barile Hill ¹⁴

Silke Nock ^{1, 2}

YUWEI LIU ^{1, 2}

Nevan J. Krogan ^{4, 5, 8, 9}

Corie Y. Ralston ¹³

Danielle Swaney ^{4, 5, 8, 9}

Adolfo García-Sastre ^{11, 12, 15, 16}

Melanie Ott ^{8, 9, 10}

Marco Vignuzzi ⁶

Peter Walter ^{1, 2}

Aashish Manglik ^{3, 4, 8, 17}

Hide authors affiliations Show authors affiliations: 17 affiliations

Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA.

University of California, San Francisco

Howard Hughes Medical Institute

Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA, USA. |

Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, CA, USA. |

⁴

Quantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA. |

⁵

Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA, USA. |

⁶

Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Institut Pasteur, 75724 Paris Cedex 15, France. |

⁷

Department of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA. |

⁸

Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA. |

⁹

J. David Gladstone Institutes, San Francisco, CA, USA. |

¹⁰

Department of Medicine, University of California San Francisco, San Francisco, CA, USA. |

¹¹

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. |

¹²

Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. |

¹³

Molecular Biophysics and Integrated Bioimaging and the Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. |

¹⁴

Cytiva Life Sciences, Marlborough, MA, USA. |

¹⁵

Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA. |

¹⁶

The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. |

¹⁷

Department of Anesthesia and Perioperative Care, University of California at San Francisco, San Francisco, CA, USA. |

Publication type: Journal Article

Publication date: 2020-12-18

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.abe3255

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Multidisciplinary

Abstract

Nanobodies that neutralize

Monoclonal antibodies that bind to the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show therapeutic promise but must be produced in mammalian cells and need to be delivered intravenously. By contrast, single-domain antibodies called nanobodies can be produced in bacteria or yeast, and their stability may enable aerosol delivery. Two papers now report nanobodies that bind tightly to spike and efficiently neutralize SARS-CoV-2 in cells. Schoof et al. screened a yeast surface display of synthetic nanobodies and Xiang et al. screened anti-spike nanobodies produced by a llama. Both groups identified highly potent nanobodies that lock the spike protein in an inactive conformation. Multivalent constructs of selected nanobodies achieved even more potent neutralization.

Science , this issue p. 1473 , p. 1479

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Schoof M. et al. An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike // Science. 2020. Vol. 370. No. 6523. pp. 1473-1479.

GOST all authors (up to 50) Copy

Schoof M. et al. An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike // Science. 2020. Vol. 370. No. 6523. pp. 1473-1479.

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@article{2020_Schoof,

author = {Michael Schoof and Bryan Faust and Reuben A Saunders and Smriti Sangwan and Veronica V Rezelj and Nick Hoppe and Morgane Boone and Christian B Billesbølle and Cristina Puchades and C. M. Azumaya and H. Kratochvil and Marcell Zimanyi and Ishan Deshpande and Jiahao Liang and Miles Sasha Dickinson and Kim Cuong Nguyen and Cynthia M Chio and Gregory E Merz and Michael C. Thompson and Devan Diwanji and Kaitlin Schaefer and Aditya A Anand and Niv Dobzinski and Beth S. Zha and Camille R. Simoneau and Kristoffer E Leon and Kris M White and Un Seng Chio and Meghna Gupta and M Jin and Fei Li and Yanxin Liu and Kaihua Zhang and David Bulkley and Ming Sun and Joel M Smith and Alexandrea Rizo and Frank R Moss and Axel F. Brilot and Sergei Pourmal and R Trenker and Thomas H Pospiech and Sayan Gupta and Benjamin Barsi Rhyne and Vladislav Belyy and Andrew W Barile Hill and Silke Nock and YUWEI LIU and Nevan J. Krogan and Corie Y. Ralston and others},

title = {An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike},

journal = {Science},

year = {2020},

volume = {370},

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

month = {dec},

url = {https://doi.org/10.1126/science.abe3255},

number = {6523},

pages = {1473--1479},

doi = {10.1126/science.abe3255}

}

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Schoof, Michael, et al. “An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike.” Science, vol. 370, no. 6523, Dec. 2020, pp. 1473-1479. https://doi.org/10.1126/science.abe3255.

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)