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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Deep geometric representations for modeling effects of mutations on protein-protein binding affinity.
TL;DR: Experiments showed that, without any annotated signals, GraphPPI can capture meaningful patterns of the protein structures and new state-of-the-art performance in predicting the binding affinity changes upon both single- and multi-point mutations on five benchmark datasets.
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Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2
Wanwisa Dejnirattisai,D. Zhou,Piyada Supasa,Chang Liu,Alexander J. Mentzer,Helen M. Ginn,Yuguang Zhao,Helen M. E. Duyvesteyn,Aekkachai Tuekprakhon,R Nutalai,Beibei Wang,Guido C. Paesen,Cesar Lopez-Camacho,J Slon-Campos,Thomas S. Walter,Donal T. Skelly,Sue Ann Costa Clemens,Sue Ann Costa Clemens,Felipe Gomes Naveca,Valdinete Alves do Nascimento,Fernanda Nascimento,Cristiano Fernandes da Costa,Paola Cristina Resende,Alex Pauvolid-Corrêa,Marilda M. Siqueira,Christina Dold,R Levin,Tao Dong,Andrew J. Pollard,Julian C. Knight,Derrick W. Crook,Teresa Lambe,Elizabeth A. Clutterbuck,S Bibi,Amy Flaxman,M Bittaye,Sandra Belij-Rammerstorfer,Sarah C. Gilbert,Miles W. Carroll,Miles W. Carroll,Paul Klenerman,Eleanor Barnes,Susanna Dunachie,Neil G. Paterson,Mark A. Williams,David Hall,Rubin Hulswit,Thomas A. Bowden,Elizabeth E. Fry,Juthathip Mongkolsapaya,Juthathip Mongkolsapaya,Jingshan Ren,David I. Stuart,Gavin R. Screaton +53 more
TL;DR: In this article, structural analysis of the SARS-CoV-2 pandemic showed that B.1.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses.
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Isolation and Characterization of Cross-Neutralizing Coronavirus Antibodies from COVID-19+ Subjects
Madeleine F. Jennewein,Anna J. MacCamy,Nicholas R. Akins,Junli Feng,Leah J. Homad,Nicholas K. Hurlburt,Emilie Seydoux,Yu-Hsin Wan,Andrew B. Stuart,Venkata Viswanadh Edara,Katharine Floyd,Abigail Vanderheiden,John R. Mascola,Nicole A. Doria-Rose,Lingshu Wang,Eun Sung Yang,Helen Y. Chu,Jonathan L. Torres,Gabriel Ozorowski,Andrew B. Ward,Rachael E. Whaley,Kristen W. Cohen,Marie Pancera,Marie Pancera,M. Juliana McElrath,M. Juliana McElrath,Janet A. Englund,Andrés Finzi,Mehul S. Suthar,Andrew T. McGuire,Andrew T. McGuire,Leonidas Stamatatos,Leonidas Stamatatos +32 more
TL;DR: In this article, the authors characterized 198 antibodies isolated from four COVID19+ subjects and identified 14 SARS-CoV-2 neutralizing antibodies, one targeted the NTD, one recognized an epitope in S2 and twelve bound the RBD.
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SARS-CoV-2 Antiviral Therapy.
TL;DR: In this article, a review summarizes 1 year of progress in the race to develop antiviral therapies for COVID-19, including research spanning preclinical and clinical drug development efforts, with an emphasis on antiviral compounds that are in clinical development or that are high priorities for clinical development.
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SARS-CoV-2: Immune Response Elicited by Infection and Development of Vaccines and Treatments.
Gisela Canedo-Marroquín,Farides Saavedra,Catalina A. Andrade,Roslye V Berrios,Linmar Rodríguez-Guilarte,Maria Cecilia Opazo,Claudia A. Riedel,Alexis M. Kalergis +7 more
TL;DR: Clinical evidence suggests that migration of immune cells to the affected organs can produce an exacerbated release of proinflammatory mediators that contribute to disease and render the immune response as a major player during the development of the COVID-19 disease.
References
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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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