An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike
Authors: Schoof Michael , Faust Bryan , Saunders Reuben A. , Sangwan Smriti , Rezelj Veronica , Hoppe Nick , Boone Morgane , Billesbølle Christian B. , Puchades Cristina , Azumaya Caleigh M. , Kratochvil Huong T. , Zimanyi Marcell , Deshpande Ishan , Liang Jiahao , Dickinson Sasha , Nguyen Henry C. , Chio Cynthia M. , Merz Gregory E. , Thompson Michael C. , Diwanji Devan , Schaefer Kaitlin , Anand Aditya A. , Dobzinski Niv , Zha Beth Shoshana , Simoneau Camille R. , Leon Kristoffer , White Kris M. , Chio Un Seng , Gupta Meghna , Jin Mingliang , Li Fei , Liu Yanxin , Zhang Kaihua , Bulkley David , Sun Ming , Smith Amber M. , Rizo Alexandrea N. , Moss Frank , Brilot Axel F. , Pourmal Sergei , Trenker Raphael , Pospiech Thomas , Gupta Sayan , Barsi-Rhyne Benjamin , Belyy Vladislav , Barile-Hill Andrew W. , Nock Silke , Liu Yuwei , Krogan Nevan J. , Ralston Corie Y. , Swaney Danielle L. , García-Sastre Adolfo , Ott Melanie , Vignuzzi Marco ,   QCRG Structural Biology Consortium, Walter Peter , Manglik Aashish , 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. 
Published: November 2020

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