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
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Cryo-EM structure of SARS-CoV-2 postfusion spike in membrane
Wei-Guo Shi,Yongfei Cai,Haisun Zhu,Hanqin Peng,Jewel Voyer,Sophia Rits-Volloch,Hong Cao,Megan L. Mayer,Kangkang Song,Chen Xu,Jianming Lu,Jun Zhang,Bing Chen +12 more
TL;DR: In this article , the intact post-fusion spike in a lipid bilayer that represents the single-membrane product of the fusion reaction was analyzed and the structure provided structural definition of the functionally critical membraneinteracting segments, including the fusion peptide and trans-brane anchor.
Journal ArticleDOI
Impact of Casirivimab-Imdevimab on Severe Acute Respiratory Syndrome Coronavirus 2 Delta Variant Nasopharyngeal Virus Load and Spike Quasispecies
Camille Vellas,Arnaud Del Bello,G. Gaube,Pauline Trémeaux,Nicolas Jeanne,Noémie Ranger,Guillaume Martin-Blondel,Pierre Delobel,Nassim Kamar,Jacques Izopet +9 more
TL;DR: Casirivimab-Imdevimab is an effective treatment for patients infected with the SARS-CoV-2 delta variant and no key mutations that reduced mAb activity in the authors' patients are detected.
Journal ArticleDOI
Molecular and Epidemiological Characterization of Emerging Immune-Escape Variants of SARS-CoV-2
Kei Miyakawa,Sundararaj Stanleyraj Jeremiah,Yutaro Yamaoka,Takahiko Koyama,Reitaro Tokumasu,Michiharu Kudo,Hideaki Kaneto,Akihide Ryo +7 more
TL;DR: The findings demonstrate the differential neutralization efficacy of the COVID-19 vaccine and monoclonal antibodies against circulating variants, suggesting the need for pandemic alerts and booster vaccinations against the currently prevalent variants.
Posted ContentDOI
Modeling mutational effects on biochemical phenotypes using convolutional neural networks: application to SARS-CoV-2
Bo Wang,Eric R. Gamazon +1 more
TL;DR: In this paper, a convolutional neural network was trained on protein sequence mutations in SARS-CoV-2's spike receptor binding domain and the human ACE2 zinc-binding peptidase domain to predict binding affinity and protein expression.
Journal ArticleDOI
Spontaneous Lower Gastrointestinal Bleeding Following Casirivimab/Imdevimab Treatment for COVID-19 Infection: A Case Presentation and Short Literature Review
Ajmera Km,Wilkinson Heather +1 more
TL;DR: The first case of life-threatening lower gastrointestinal bleeding potentially related to REGNCOV2 treatment is presented, and the efficacy and safety of mAbs are well documented.
References
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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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