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

doi:10.1126/science.abe3255

GSTDTAP > 气候变化

DOI	10.1126/science.abe3255
	An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike
	Michael Schoof; Bryan Faust; Reuben A. Saunders; Smriti Sangwan; Veronica 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 A. Anand; Niv Dobzinski; Beth Shoshana Zha; Camille R. Simoneau; Kristoffer 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 Moss; Axel F. Brilot; Sergei Pourmal; Raphael Trenker; Thomas 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; Melanie Ott; Marco Vignuzzi; QCRG Structural Biology Consortium4‡; Peter Walter; Aashish Manglik
	2020-12-18
发表期刊	Science
出版年	2020
英文摘要	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][1], p. [1479][2] The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryo–electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains locked into their inaccessible down state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains function after aerosolization, lyophilization, and heat treatment, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia. [1]: /lookup/doi/10.1126/science.abe3255 [2]: /lookup/doi/10.1126/science.abe4747
领域	气候变化 ; 资源环境
URL	查看原文
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/308369
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Michael Schoof,Bryan Faust,Reuben A. Saunders,et al. An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike[J]. Science,2020.
APA	Michael Schoof.,Bryan Faust.,Reuben A. Saunders.,Smriti Sangwan.,Veronica Rezelj.,...&Aashish Manglik.(2020).An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike.Science.
MLA	Michael Schoof,et al."An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike".Science (2020).