An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike
Michael Schoof,Bryan Faust,R.A. Saunders,Smriti Sangwan,Veronica V. Rezelj,Nick Hoppe,Morgane Boone,Christian B. Billesbølle,Cristina Puchades,Caleigh M. Azumaya,Huong T. Kratochvil,M. Zimanyi,Ishan Deshpande,Jiahao Liang,S. Dickinson,Henry C. Nguyen,Cynthia M. Chio,Gregory E. Merz,Michael C. Thompson,Devan Diwanji,Kaitlin Schaefer,Aditya A. Anand,Niv Dobzinski,Beth S. Zha,Camille R. Simoneau,Camille R. Simoneau,Kristoffer E. Leon,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,A.W. Barile-Hill,Silke Nock,Yuwei Liu,Nevan J. Krogan,Corie Y. Ralston,Danielle L. Swaney,Adolfo García-Sastre,Melanie Ott,Melanie Ott,Marco Vignuzzi,Peter Walter,Aashish Manglik +58 more
TLDR
Nanobodies that bind tightly to spike and efficiently neutralize SARS-CoV-2 in cells are reported, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia.Abstract:
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.read more
Citations
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Studying SARS-CoV-2 with Fluorescence Microscopy.
TL;DR: In this paper, the authors review the use of fluorescence microscopy to study SARS-CoV-2 and related viruses and discuss the prospects for the application of recently developed advanced methods for fluorescence labeling and microscopy.
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Single-domain near-infrared protein provides a scaffold for antigen-dependent fluorescent nanobodies
Olena S. Oliinyk,Mikhail Baloban,Charles L. Clark,Erin M. Carey,Sergei V. Pletnev,Axel Nimmerjahn,Vladislav V. Verkhusha +6 more
TL;DR: In this paper , a 17 kDa NIR fluorescent protein (FP) called miRFP670nano3 was used as an internal tag for deep-brain imaging, which can be used to detect and manipulate cellular targets.
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50 Years of Structural Immunology.
Ian A. Wilson,Robyn L. Stanfield +1 more
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Book ChapterDOI
Antibody-mediated immunity to SARS-CoV-2 spike
TL;DR: In this paper , the structure and function of spike, polyclonal immunity to SARS-CoV-2 spike, and the emergence of major variants that evade immunity are discussed.
Journal ArticleDOI
Single-domain near-infrared protein provides a scaffold for antigen-dependent fluorescent nanobodies
Olena S. Oliinyk,Mikhail Baloban,Charles L. Clark,Erin M. Carey,Sergei V. Pletnev,Axel Nimmerjahn,Vladislav V. Verkhusha +6 more
TL;DR: In this paper , a 17 kDa NIR fluorescent protein (FP) called miRFP670nano3 was used as an internal tag for deep-brain imaging, which can be used to detect and manipulate cellular targets.
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