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

2020; American Association for the Advancement of Science; Volume: 370; Issue: 6523 Linguagem: Inglês

10.1126/science.abe3255

1095-9203

Michael Schoof, Bryan Faust, Reuben A. Saunders, Smriti Sangwan, Veronica V. Rezelj, Nick Hoppe, Morgane Boone, Christian B. Billesbølle, Cristina Puchades, Caleigh M. Azumaya, Huong T. Kratochvil, Marcell Zimanyi, Ishan Deshpande, Jiahao Liang, Sasha Dickinson, Henry C. Nguyen, Cynthia M. Chio, Gregory E. Merz, Michael C. Thompson, Devan Diwanji, Kaitlin Schaefer, Aditya Anand, Niv Dobzinski, Beth Shoshana Zha, Camille R. Simoneau, Kristoffer E. Leon, Kris M. White, Un Seng Chio, Meghna Gupta, Mingliang Jin, Fei Li, Yanxin Liu, Kaihua Zhang, David Bulkley, Ming Sun, Amber M. Smith, Alexandrea N. Rizo, Frank R. Moss, Axel F. Brilot, Sergei Pourmal, Raphael Trenker, Thomas H. Pospiech, Sayan Gupta, Benjamin Barsi‐Rhyne, Vladislav Belyy, Andrew W. Barile-Hill, Silke Nock, Yuwei Liu, Nevan J. Krogan, Corie Y. Ralston, Danielle L. Swaney, Adolfo García‐Sastre, Mélanie Ott, Marco Vignuzzi, Peter Walter, Aashish Manglik, Caleigh M. Azumaya, Cristina Puchades, Ming Sun, Julian R. Braxton, Axel F. Brilot, Meghna Gupta, Fei Li, Kyle E. Lopez, Arthur A. Melo, Gregory E. Merz, Frank R. Moss, Joana Paulino, Thomas H. Pospiech, Sergei Pourmal, Alexandrea N. Rizo, Amber M. Smith, Paul V. Thomas, Feng Wang, Zanlin Yu, Miles Sasha Dickinson, Henry C. Nguyen, Daniel Asarnow, Melody G. Campbell, Cynthia M. Chio, Un Seng Chio, Devan Diwanji, Bryan Faust, Meghna Gupta, Nick Hoppe, Mingliang Jin, Junrui Li, Yanxin Liu, Gregory E. Merz, Smriti Sangwan, Tsz Kin Martin Tsui, Raphael Trenker, Donovan Trinidad, Eric Tse, Kaihua Zhang, Fengbo Zhou, Nadia Herrera, Huong T. Kratochvil, Ursula Schulze‐Gahmen, Michael C. Thompson, I.D. Young, J.T. Biel, Ishan Deshpande, Xi Liu, Christian B. Billesbølle, Carlos Nowotny, Amber M. Smith, Jianhua Zhao, Alisa Bowen, Nick Hoppe, Yen-Li Li, Phuong Nguyen, Mali Safari, Kaitlin Schaefer, Natalie Whitis, Michelle Moritz, Tristan W. Owens, Amy Diallo, Kate Kim, Jessica K. Peters, Erron W. Titus, Jenny Chen, Loan Doan, Sebastián Flores, Victor L. Lam, Li Yang, Megan Lo, Aye C. Thwin, Stephanie A. Wankowicz, Sunny Zhang, David Bulkley, Arceli Joves, Almarie Joves, Liam McKay, Mariano Tabios, Oren S. Rosenberg, Kliment A. Verba, David A. Agard, Yifan Cheng, James S. Fraser, Adam Frost, Natalia Jura, Tanja Kortemme, Nevan J. Krogan, Aashish Manglik, Daniel R. Southworth, Robert M. Stroud,

Molecular Communication and Nanonetworks

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