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
Structural Biology of Nanobodies against the Spike Protein of SARS-CoV-2
Qilong Tang,Qilong Tang,Raymond J. Owens,Raymond J. Owens,James H. Naismith,James H. Naismith +5 more
TL;DR: In this article, the structural features that guide the nanobody recognition of the receptor binding domain of the Spike protein of SARS-CoV-2 have been discussed, and a few agents have completed animal trials with very encouraging results showing their potential for treating infection.
Journal ArticleDOI
The Role and Uses of Antibodies in COVID-19 Infections: A Living Review
D Oliver Scourfield,Sophie G. Reed,Max Quastel,Jennifer Alderson,Valentina M T Bart,Alicia Teijeira Crespo,Ruth Jones,Ellie Pring,Felix Richter,Stephanie E A Burnell +9 more
TL;DR: A review of the major aspects of SARS-CoV-2-specific antibody research can be found in this paper, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity.
Journal ArticleDOI
Co-evolution of interacting proteins through non-contacting and non-specific mutations
TL;DR: This paper identified all possible single substitutions in a bacterial toxin-antitoxin system that enable it to tolerate otherwise interface-disrupting mutations in its antitoxin, despite covariation in homologues occurring primarily between specific pairs of contacting residues across the interface.
Posted ContentDOI
Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants
Liang Qu,Zongyi Yi,Yong Shen,Yiyuan Xu,Zeguang Wu,Huixian Tang,Xia Xiao,Xiaojing Dong,Li Guo,Ayijiang Yisimayi,Y Cao,Zhuo Zhou,Jianwei Wang,Xiaoliang Sunney Xie,Wensheng Wei +14 more
TL;DR: In this article, a circular RNA (circRNA) vaccine that encodes the trimeric RBD of SARS-CoV-2 spike protein was reported, which could be rapidly produced via in vitro transcription and is highly stable without nucleotide modification.
Posted ContentDOI
Synthetic nanobody-SARS-CoV-2 receptor-binding domain structures identify distinct epitopes
TL;DR: X-ray crystal structures of three synthetic nanobodies (sybodies) (Sb16, Sb45 and Sb68) were reported in this article, which reveal details of CDR loop interactions in recognition of distinct epitopic sites.
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