An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike-Reference-Cited by-同舟云学术

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

Published:2020-12-18 Issue:6523 Volume:370 Page:1473-1479
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Schoof Michael¹²^ORCID,Faust Bryan¹²³⁴^ORCID,Saunders Reuben A.¹⁵^ORCID,Sangwan Smriti¹²^ORCID,Rezelj Veronica⁶^ORCID,Hoppe Nick³⁴^ORCID,Boone Morgane¹²^ORCID,Billesbølle Christian B.³⁴^ORCID,Puchades Cristina⁴^ORCID,Azumaya Caleigh M.⁴^ORCID,Kratochvil Huong T.⁴^ORCID,Zimanyi Marcell¹²^ORCID,Deshpande Ishan³⁴^ORCID,Liang Jiahao³^ORCID,Dickinson Sasha⁴^ORCID,Nguyen Henry C.⁴^ORCID,Chio Cynthia M.⁴^ORCID,Merz Gregory E.⁴^ORCID,Thompson Michael C.⁴^ORCID,Diwanji Devan⁴^ORCID,Schaefer Kaitlin⁴^ORCID,Anand Aditya A.¹²^ORCID,Dobzinski Niv¹²^ORCID,Zha Beth Shoshana⁷^ORCID,Simoneau Camille R.⁸⁹¹⁰^ORCID,Leon Kristoffer⁸⁹¹⁰^ORCID,White Kris M.¹¹¹²^ORCID,Chio Un Seng⁴^ORCID,Gupta Meghna⁴^ORCID,Jin Mingliang⁴^ORCID,Li Fei⁴^ORCID,Liu Yanxin⁴^ORCID,Zhang Kaihua⁴^ORCID,Bulkley David⁴^ORCID,Sun Ming⁴^ORCID,Smith Amber M.⁴^ORCID,Rizo Alexandrea N.⁴^ORCID,Moss Frank⁴^ORCID,Brilot Axel F.⁴^ORCID,Pourmal Sergei⁴^ORCID,Trenker Raphael⁴^ORCID,Pospiech Thomas⁴^ORCID,Gupta Sayan¹³,Barsi-Rhyne Benjamin³,Belyy Vladislav¹²^ORCID,Barile-Hill Andrew W.¹⁴,Nock Silke¹²,Liu Yuwei¹²,Krogan Nevan J.⁴⁵⁸⁹^ORCID,Ralston Corie Y.¹³,Swaney Danielle L.⁴⁵⁸⁹^ORCID,García-Sastre Adolfo¹¹¹²¹⁵¹⁶^ORCID,Ott Melanie⁸⁹¹⁰^ORCID,Vignuzzi Marco⁶^ORCID,Walter Peter¹²^ORCID,Manglik Aashish³⁴⁸¹⁷^ORCID,Azumaya Caleigh M.,Puchades Cristina,Sun Ming,Braxton Julian R.,Brilot Axel F.,Gupta Meghna,Li Fei,Lopez Kyle E.,Melo Arthur,Merz Gregory E.,Moss Frank,Paulino Joana,Pospiech Thomas H.,Pourmal Sergei,Rizo Alexandrea N.,Smith Amber M.,Thomas Paul V.,Wang Feng,Yu Zanlin,Dickinson Miles Sasha,Nguyen Henry C.,Asarnow Daniel,Campbell Melody G.,Chio Cynthia M.,Chio Un Seng,Diwanji Devan,Faust Bryan,Gupta Meghna,Hoppe Nick,Jin Mingliang,Li Junrui,Liu Yanxin,Merz Gregory E.,Sangwan Smriti,Tsui Tsz Kin Martin,Trenker Raphael,Trinidad Donovan,Tse Eric,Zhang Kaihua,Zhou Fengbo,Herrera Nadia,Kratochvil Huong T.,Schulze-Gahmen Ursula,Thompson Michael C.,Young Iris D.,Biel Justin,Deshpande Ishan,Liu Xi,Billesbølle Christian Bache,Nowotny Carlos,Smith Amber M.,Zhao Jianhua,Bowen Alisa,Hoppe Nick,Li Yen-Li,Nguyen Phuong,Safari Mali,Schaefer Kaitlin,Whitis Natalie,Moritz Michelle,Owens Tristan W.,Diallo Amy,Kim Kate,Peters Jessica K.,Titus Erron W.,Chen Jenny,Doan Loan,Flores Sebastian,Lam Victor L.,Li Yang,Lo Megan,Thwin Aye C.,Wankowicz Stephanie,Zhang Yang,Bulkley David,Joves Arceli,Joves Almarie,McKay Liam,Tabios Mariano,Rosenberg Oren S.,Verba Kliment A.,Agard David A.,Cheng Yifan,Fraser James S.,Frost Adam,Jura Natalia,Kortemme Tanja,Krogan Nevan J.,Manglik Aashish,Southworth Daniel R.,Stroud Robert M.,

Affiliation:

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

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

3. 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.

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

Funder

National Institutes of Health

Howard Hughes Medical Institute

National Institute of Allergy and Infectious Diseases

U.S. Department of Education

Defense Sciences Office, DARPA

Searle Scholars Program

Pew Charitable Trusts

JPB Foundation

Roddenberry Foundation

Helen Hay Whitney Foundation

Damon Runyon Cancer Research Foundation