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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REGEN-COV ® antibody cocktail bioanalytical strategy: comparison of LC-MRM-MS and immunoassay methods for drug quantification.
Susan C Irvin,Samit Ganguly,Rachel Weiss,Chinnasamy Elango,Xuefei Zhong,Yuan Mao,Hong Yan,Ning Li,Giane Sumner,Kenneth C. Turner,John D. Davis,A. Thomas DiCioccio,Matthew Andisik,Michael A Partridge,Albert Torri +14 more
TL;DR: In this paper, a two-part bioanalytical strategy was implemented to ensure the anti-SARS-CoV-2 monoclonal antibody cocktail, REGEN-COV (RONAPREVE® outside the USA).
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Two-step strategy for the identification of SARS-CoV-2 variants co-occurring with spike deletion H69-V70, Lyon, France, August to December 2020
Antonin Bal,Grégory Destras,Alexandre Gaymard,Hadrien Regue,Quentin Semanas,Constance d'Aubarede,Geneviève Billaud,Frédéric Laurent,Claudia González,M. Valette,M. Bouscambert,Bruno Lina,Florence Morfin,Laurence Josset +13 more
TL;DR: In this paper, the authors report the implementation of a two-step strategy enabling to detect SARS-CoV-2 variants carrying H69-V70 deletion, which resulted in a false negative result for the spike target of a three-target RT-PCR assay.
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Effect of an Inhibitor on the ACE2-Receptor-Binding Domain of SARS-CoV-2
TL;DR: The current study increases the understanding of ACE inhibition by MLN-4760 and how it modulates the conformational properties of ACE2 and its interaction with the receptor-binding domain (RBD) of SARS-CoV-2.
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Persistent SARS-CoV-2 Infection in a Patient With Non-hodgkin Lymphoma: Intra-Host Genomic Diversity Analysis
Angelica Bianco,Loredana Capozzi,Laura Del Sambro,Domenico Simone,Lorenzo Pace,Valeria Rondinone,Laura Difato,Angela Miccolupo,Caterina Manzari,A. L. Fedele,Antonio Parisi +10 more
TL;DR: The findings show the evolution of the intra-host variability during the course of a long-lasting infection with severe acute respiratory syndrome coronavirus 2.
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Microalgae as an Efficient Vehicle for the Production and Targeted Delivery of Therapeutic Glycoproteins against SARS-CoV-2 Variants
Jaber Dehghani,Ali Movafeghi,Elodie Mathieu-Rivet,Narimane Mati-Baouche,Sébastien Calbo,Patrice Lerouge,Muriel Bardor +6 more
TL;DR: Because microalgal cells contain a rigid cell wall that could act as a natural encapsulation to protect the recombinant proteins from the aggressive environment of the stomach, this feature could be used for the rapid production and edible targeted delivery of S-glycoprotein and soluble ACE2 for the treatment/inhibition of SARS-CoV-2.
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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