Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies.
Alina Baum,Benjamin O. Fulton,Elzbieta Wloga,Richard Copin,Kristen E. Pascal,Vincenzo Russo,Stephanie Giordano,Kathryn Lanza,Nicole Negron,Min Ni,Yi Wei,Gurinder S. Atwal,Andrew J. Murphy,Neil Stahl,George D. Yancopoulos,Christos A. Kyratsous +15 more
TLDR
This work investigated the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails.Abstract:
Antibodies targeting the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present a promising approach to combat the coronavirus disease 2019 (COVID-19) pandemic; however, concerns remain that mutations can yield antibody resistance. We investigated the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails. These antibodies remain effective against spike variants that have arisen in the human population. However, novel spike mutants rapidly appeared after in vitro passaging in the presence of individual antibodies, resulting in loss of neutralization; such escape also occurred with combinations of antibodies binding diverse but overlapping regions of the spike protein. Escape mutants were not generated after treatment with a noncompeting antibody cocktail.read more
Citations
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Journal ArticleDOI
Antibody-mediated neutralization of SARS-CoV-2
Henning Gruell,Kanika Vanshylla,Timm Weber,Christopher O. Barnes,Christoph Kreer,Florian Klein +5 more
TL;DR: A review of the development, function, and potential use of neutralizing antibodies to prevent and treat CoV-2-associated coronavirus disease 2019 (COVID-19) can be found in this paper .
Journal ArticleDOI
Comparative Perturbation-Based Modeling of the SARS-CoV-2 Spike Protein Binding with Host Receptor and Neutralizing Antibodies: Structurally Adaptable Allosteric Communication Hotspots Define Spike Sites Targeted by Global Circulating Mutations.
TL;DR: In this article, the role of functional residues in the SARS-CoV-2 spike protein was examined using an integrative computational approach to examine molecular mechanisms and determine functional signatures underlying the role in functional residues.
Journal ArticleDOI
A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection.
Hejun Liu,Meng Yuan,Deli Huang,Sandhya Bangaru,Fangzhu Zhao,Chang-Chun D Lee,Linghang Peng,Shawn Barman,Xueyong Zhu,David Nemazee,Dennis R. Burton,Dennis R. Burton,Marit J. van Gils,Rogier W. Sanders,Rogier W. Sanders,Hans Christian Kornau,Hans Christian Kornau,S. Momsen Reincke,S. Momsen Reincke,S. Momsen Reincke,Harald Prüss,Harald Prüss,Harald Prüss,Jakob Kreye,Nicholas C. Wu,Andrew B. Ward,Ian A. Wilson +26 more
TL;DR: In this article, the crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS -CoV.
Journal ArticleDOI
Structural basis for accommodation of emerging B.1.351 and B.1.1.7 variants by two potent SARS-CoV-2 neutralizing antibodies.
Gabriele Cerutti,Micah Rapp,Yicheng Guo,Fabiana Bahna,Jude Bimela,Eswar R. Reddem,Jian Yu,Pengfei Wang,Lihong Liu,Yaoxing Huang,David D. Ho,Peter D. Kwong,Zizhang Sheng,Lawrence Shapiro +13 more
TL;DR: In this article, the neutralization potency of two antibodies, 1-57 and 2-7, which target the receptor-binding domain (RBD) of the spike, was unaffected by emerging SARS-CoV-2 strains.
Journal ArticleDOI
Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers.
Edurne Rujas,Iga Kucharska,Yong Zi Tan,Samir Benlekbir,Hong Cui,Tiantian Zhao,Gregory A. Wasney,Patrick Budylowski,Furkan Guvenc,Jocelyn C. Newton,Taylor Sicard,Anthony Semesi,Krithika Muthuraman,Amy Nouanesengsy,Clare Burn Aschner,Katherine Prieto,Stephanie A. Bueler,Sawsan Youssef,Sindy Liao-Chan,Jacob Glanville,Natasha Christie-Holmes,Samira Mubareka,Scott D. Gray-Owen,John L. Rubinstein,Bebhinn Treanor,Jean-Philippe Julien +25 more
TL;DR: In this paper, the human apoferritin protomer is used as a modular subunit to drive oligomerization of antibody fragments and transform antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers.
References
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TL;DR: Cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein of SARS-CoV-2 are presented, providing important insights into the molecular basis for coronavirus recognition and infection.
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TL;DR: The crystal structure of the C-terminal domain of SARS-CoV-2 (SARS- coV- 2-CTD) spike (S) protein in complex with human ACE2 (hACE2) is presented, which reveals a hACE2-binding mode similar overall to that observed for SARS -CoV.
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Journal ArticleDOI
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
TL;DR: Several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which was identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS- coV) in 2003, and one antibody (named S309) potently neutralization, which may limit the emergence of neutralization-escape mutants.
Journal ArticleDOI
Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells.
Y Cao,Bin Su,Xianghua Guo,Wenjie Sun,Yong-Qiang Deng,Linlin Bao,Qinyu Zhu,Xu Zhang,Yinghui Zheng,Chenyang Geng,Xiaoran Chai,Runsheng He,Xiaofeng Li,Qi Lv,Hua Zhu,Wei Deng,Yanfeng Xu,Yanjun Wang,Luxin Qiao,Yafang Tan,Liyang Song,Guopeng Wang,Xiao-Xia Du,Ning Gao,Jiangning Liu,Junyu Xiao,Xiao-Dong Su,Zongmin Du,Yingmei Feng,Chuan Qin,Cheng-Feng Qin,Ronghua Jin,X. Sunney Xie +32 more
TL;DR: It is shown that human neutralizing antibodies could be efficiently discovered by high-throughput single B-cell sequencing in response to pandemic infectious diseases.
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