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
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Journal ArticleDOI
Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections
Ching-Yee Loo,Qi Tony Zhou +1 more
TL;DR: In this paper , the authors discussed the recent advances in the inhalation strategies of nano-formulations that target virus respiratory infections and discussed the use of nanotechnology coupled with a needle-free administration approach for the delivery of complex therapeutics to treat respiratory infections.
Book ChapterDOI
Controlling ion channel trafficking by targeted ubiquitination and deubiquitination.
TL;DR: Target ubiquitination and deubiquitination approaches are developed that enable selective posttranslational down- or up-regulation, respectively, of desired ion channels and are presented as potential therapeutics and useful research tools.
Posted ContentDOI
Hetero-bivalent Nanobodies Provide Broad-spectrum Protection against SARS-CoV-2 Variants of Concern including Omicron
Kamini Sharma & Dr. Surender Kumar Sharma,Ramiro David Jacobo Galván,James P Allen,Kelvin Everest +3 more
TL;DR: In this paper , two hetero-bivalent nanobodies were developed with potent neutralization against original WT SARS-CoV-2, termed aRBD-2-5/aRBD2-7, by fusing the RBD2 with either a RBD-5 or aR BD-7.
Journal ArticleDOI
A Novel Fusion Protein System for the Production of Nanobodies and the SARS-CoV-2 Spike RBD in a Bacterial System
Dóra Nagy-Fazekas,Pál Stráner,Péter Ecsédi,Nóra Taricska,Adina Borbély,László Nyitray,András Perczel +6 more
TL;DR: In this paper , a bacterial expression system that allows an easy, fast, and cost-effective way to prepare nanobodies was presented, using ecotin as a periplasmic translocator and a passive refolding chaperone.
Journal ArticleDOI
Screening, Expression, and Identification of Nanobody against SARS-CoV-2 Spike Protein
Qianling Su,Wei Shi,Xianing Huang,Yakun Wan,Guanghui Li,Bengang Xing,Zhi Ping Xu,Hongbo Liu,Bruce D. Hammock,Xiaomei Yang,Shihua Yin,Xiaoling Lu +11 more
TL;DR: This study screened and yielded specific nanobodies (Nbs) against SARS-CoV-2 spike protein receptor binding domain (RBD), following testing its basic characteristics, laying an essential foundation for further research as well as the applications of diagnostic and therapeutic tools of Sars-Cov-2.
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