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
More filters
Journal ArticleDOI
Targeted Alpha Therapy (TAT) with Single-Domain Antibodies (Nanobodies)
Kate Hurley,Meiyun Cao,Yi Wang +2 more
TL;DR: In this article , a review of recent advancements in the use of nanobodies as a vehicle for targeted alpha therapy (TαT) is presented, highlighting recent studies involving nanobody-based TαT.
Journal ArticleDOI
Regulating the microenvironment with nanomaterials: Potential strategies to ameliorate COVID-19
Zhicheng Liu,Zhuolei Han,Xin Jin,Jusung An,Jae-Wan Kim,Wenting Chen,Jong Seung Kim,Ji Zheng,Jun Deng +8 more
TL;DR: In this paper , a review systematically discusses alterations of homeostasis in COVID-19 patients and potential mechanisms and discusses the challenges and prospects of using nanomaterials for COVID19 management.
Posted ContentDOI
A potent alpaca-derived nanobody that neutralizes SARS-CoV-2 variants
TL;DR: In this article , an alpaca-derived heavy chain antibody fragment (VHH), saRBD-1, was proposed to disrupt the SARS-CoV-2 interaction by competitively binding to the spike protein receptor-binding domain.
Posted ContentDOI
An alpaca-derived nanobody recognizes a unique conserved epitope and retains potent activity against the SARS-CoV-2 omicron variant
TL;DR: In this paper , the RBD-specific nanobody W25, which was previously isolated from an alpaca, showed superior neutralization activity towards Omicron lineage BA.1 in comparison to all other SARS-CoV2 variants.
Journal ArticleDOI
Targeted photodynamic neutralization of SARS-CoV-2 mediated by singlet oxygen
TL;DR: In this paper , a targeted photodynamic approach was developed to neutralize SARS-CoV-2 by engineering a genetically encoded photosensitizer (SOPP3) to a diverse list of antibodies targeting the wild-type (WT) spike protein, including human antibodies isolated from a 2003 SeARS (SARS) patient, potent monomeric and multimeric nanobodies targeting receptor-binding domain (RBD), and non-neutralizing antibodies (non-NAbs) targeting the more conserved N-terminal domain (NTD).
References
More filters
Journal ArticleDOI
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Chaolin Huang,Yeming Wang,Xingwang Li,Lili Ren,Jianping Zhao,Yi Hu,Li Zhang,Guohui Fan,Jiuyang Xu,Xiaoying Gu,Zhenshun Cheng,Ting Yu,Jia'an Xia,Yuan Wei,Wenjuan Wu,Xuelei Xie,Wen Yin,Li Hui,Min Liu,Yan Xiao,Hong Gao,Li Guo,Jungang Xie,Guang-Fa Wang,Rongmeng Jiang,Zhancheng Gao,Qi Jin,Jianwei Wang,Bin Cao +28 more
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
Journal ArticleDOI
Coot: model-building tools for molecular graphics.
Paul Emsley,Kevin Cowtan +1 more
TL;DR: CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality graphics.
Journal ArticleDOI
A Novel Coronavirus from Patients with Pneumonia in China, 2019.
Na Zhu,Dingyu Zhang,Wenling Wang,Xingwang Li,Bo Yang,Jingdong Song,Xiang Zhao,Baoying Huang,Weifeng Shi,Roujian Lu,Peihua Niu,Faxian Zhan,Xuejun Ma,Dayan Wang,Wenbo Xu,Wenbo Xu,Guizhen Wu,George F. Gao,Wenjie Tan +18 more
TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Journal ArticleDOI
PHENIX: a comprehensive Python-based system for macromolecular structure solution
Paul D. Adams,Paul D. Adams,Pavel V. Afonine,Gábor Bunkóczi,Vincent B. Chen,Ian W. Davis,Nathaniel Echols,Jeffrey J. Headd,Li-Wei Hung,Gary J. Kapral,Ralf W. Grosse-Kunstleve,Airlie J. McCoy,Nigel W. Moriarty,Robert D. Oeffner,Randy J. Read,David S. Richardson,Jane S. Richardson,Thomas C. Terwilliger,Peter H. Zwart +18 more
TL;DR: The PHENIX software for macromolecular structure determination is described and its uses and benefits are described.
Journal ArticleDOI
Phaser crystallographic software
Airlie J. McCoy,Ralf W. Grosse-Kunstleve,Paul D. Adams,Martyn Winn,Laurent C. Storoni,Randy J. Read +5 more
TL;DR: A description is given of Phaser-2.1: software for phasing macromolecular crystal structures by molecular replacement and single-wavelength anomalous dispersion phasing.
Related Papers (5)
SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies.
Christopher O. Barnes,Claudia A. Jette,Morgan E. Abernathy,Kim Marie A. Dam,Shannon R. Esswein,Harry B. Gristick,Andrey G. Malyutin,Naima G. Sharaf,Kathryn E. Huey-Tubman,Yu E. Lee,Davide F. Robbiani,Davide F. Robbiani,Michel C. Nussenzweig,Michel C. Nussenzweig,Anthony P. West,Pamela J. Bjorkman +15 more
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody.
Dora Pinto,Young-Jun Park,Martina Beltramello,Alexandra C. Walls,M. Alejandra Tortorici,M. Alejandra Tortorici,Siro Bianchi,Stefano Jaconi,Katja Culap,Fabrizia Zatta,Anna De Marco,Alessia Peter,Barbara Guarino,Roberto Spreafico,Elisabetta Cameroni,James Brett Case,Rita E. Chen,Colin Havenar-Daughton,Gyorgy Snell,Amalio Telenti,Herbert W. Virgin,Antonio Lanzavecchia,Michael S. Diamond,Katja Fink,David Veesler,Davide Corti +25 more