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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A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients by phage display is binding to the ACE2-RBD interface and is tolerant to most known recently emerging RBD mutations
Federico Bertoglio,Viola Fühner,Maximilian Ruschig,Philip Alexander Heine,Leila Abasi,Thomas Klünemann,Ulfert Rand,Doris Meier,Nora Langreder,Stephan Steinke,Rico Ballmann,Kai-Thomas Schneider,Kristian Daniel Ralph Roth,Philipp Kuhn,Peggy Riese,Dorina Schäckermann,Janin Korn,Allan Koch,M. Zeeshan Chaudhry,Kathrin Eschke,Yeonsu Kim,Susanne Zock-Emmenthal,Marlies Becker,Margitta Scholz,Gustavo Marçal Schmidt Garcia Moreira,Esther Veronika Wenzel,Giulio Russo,Hendrikus S.P. Garritsen,Sebastian Casu,Andreas Gerstner,Günter Roth,Julia Adler,Jakob Trimpert,Andreas Hermann,Thomas Schirrmann,Stefan Dübel,André Frenzel,Joop van den Heuvel,Luka Cicin-Sain,Maren Schubert,Michael Hust +40 more
TL;DR: In this article, a recombinant human antibody called STE90-C11 was used to neutralize SARS-CoV-2 virus in vitro and in vivo and the crystal structure was solved at 2.1.0 A resolution showing that the antibody binds at the same region as ACE2 to RBD.
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Sensing of COVID-19 Antibodies in Seconds via Aerosol Jet Printed Three Dimensional Electrodes
Azahar Ali,Chunshan Hu,Sanjida Jahan,Bin Yuan,Mohammad Sadeq Saleh,Enguo Ju,Shou-Jiang Gao,Rahul Panat +7 more
TL;DR: S1 protein sensing of its antibodies is specific, which cross-reacts neither with other antibodies nor with proteins such as Nucleocapsid antibody and Interleukin-6 protein, which will benefit the public health.
Journal ArticleDOI
Selective Pressure-Free Treatments for COVID-19
TL;DR: The pros and cons of antiviral drugs from the selective pressure and possible drug resistance point of view are discussed and the key advantages of potential selective pressure-free treatment methods such as the use of sparsely and densely ionizing low-dose radiation (LDR) are addressed.
Journal ArticleDOI
Anti-SARS-CoV-1 and −2 nanobody engineering towards avidity-inspired therapeutics
TL;DR: In this paper, the authors discuss novel approaches for the design of anti-SARS-CoV-1 and -2 nanobodies to facilitate advanced innovations in treatment technologies and suggest multivalent protein nanotechnology and chemistry approaches to translate mere molecular affinity into avidity.
Posted ContentDOI
Characterization of structural and energetic differences between conformations of the SARS-CoV-2 spike protein
Rodrigo A. Moreira,Horacio V. Guzman,Subramanian Boopathi,Subramanian Boopathi,Joseph L. Baker,Adolfo B. Poma +5 more
TL;DR: The protein structural stabilityBased on the computational determination of the dynamic contact map and the energetic difference of the spike protein conformations via the mapping of the hydration free energy by the Poisson-Boltzmann method, this result is expected to foster the discussion of the number of RBD involved during recognition and the repurposing of new drugs to disable the recognition.
References
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Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2.
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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TL;DR: Most convalescent plasma samples obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity, and rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
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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