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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Superimmunity by pan-sarbecovirus nanobodies
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TL;DR: In this paper , a pan-sarbecovirus nanobodies (psNbs) were developed to target small, flat, and flexible epitopes that contain over 75% of conserved RBD surface residues.
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Shiran Su,Thomas J. Esparza,Duong T. Nguyen,Simone Mastrogiacomo,Joong H. Kim,David L. Brody +5 more
TL;DR: In this article, an efficient near-infrared (NIR) imaging method was established to monitor VHH and VHH conjugated nanoparticle kinetics in mice using a hybrid approach.
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Binding Mechanism of Neutralizing Nanobodies Targeting SARS-CoV-2 Spike Glycoprotein.
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Structural basis of nanobodies neutralizing SARS-CoV-2 variants
Zhenzhong Shi,Xiyang Li,Luxiao Wang,Zeng Hui Sun,Haiwei Zhang,Xiaochen Chen,Q. Cui,Huarui Qiao,Zijiang Lan,Xin Zhang,Xianheng Li,Lingyun Li,Jianfeng Xu,Rui Gong,Chengpeng Fan,Yong Geng +15 more
TL;DR: In this article , a group of high-affinity nanobodies from camels immunized with receptor-binding domain (RBD) of SARS-CoV-2 spike protein was identified and resolved the structures of two noncompeting nanobogens (NB1A7 and NB1B11) in complex with RBD using X-ray crystallography.
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DNA aptamers inhibit SARS-CoV-2 spike-protein binding to hACE2 by an RBD- independent or dependent approach
Achut P. Silwal,Siddhartha Kalpa Samadhi Thennakoon,S. P. Arya,R. Postema,Raunak Jahan,Chien Minh Tran Phuoc,Xiaohong Tan +6 more
TL;DR: The strategies, which discovered aptamer inhibitors targeting the highly conserved S2-protein, as well as the design of fusion aptamers, can be used to target new coronaviruses as they emerge.
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