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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Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Peter Horby,M Mafham,Leon Peto,Mark Campbell,Guilherme Pessoa-Amorim,Enti Spata,Natalie Staplin,Jonathan Emberson,B Prudon,Paul Hine,Tom Brown,Christopher A Green,Rahuldeb Sarkar,P Desai,Bryan Yates,Tom Bewick,Simon Tiberi,Timothy Felton,Kenneth Baillie,Maya H Buch,Lucy C Chappell,Jeremy N. Day,Saul N. Faust,Thomas Jaki,Katie Jeffery,Edmund Juszczak,Wei Shen Lim,Alan A Montgomery,Andrew D Mumford,Kathy Rowan,G Thwaites,David M. Weinreich,Richard Haynes,Martin J Landray +33 more
TL;DR: In this article, the authors evaluated the efficacy and safety of a combination of two monoclonal antibodies (casirivimab and imdevimab) that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike protein.
Journal ArticleDOI
The Spike of Concern-The Novel Variants of SARS-CoV-2.
Anna Winger,Thomas Caspari +1 more
TL;DR: A review of spike mutations can be found in this paper, where the D614G mutation is the hallmark of all variants, as it promotes viral spread by increasing the number of open spike protomers in the homo-trimeric receptor complex.
Journal ArticleDOI
Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial.
Ruanne V. Barnabas,Elizabeth R. Brown,Anna Bershteyn,Helen C. Stankiewicz Karita,Christine Johnston,Lorna E. Thorpe,Angelica Kottkamp,Kathleen M. Neuzil,Miriam K. Laufer,Meagan E. Deming,Michael K. Paasche-Orlow,Patricia Kissinger,Alfred Luk,Kristopher M Paolino,Raphael J. Landovitz,Risa M Hoffman,Torin T Schaafsma,Meighan Krows,Katherine K. Thomas,Susan Morrison,Harald S. Haugen,Lara Kidoguchi,Mark H. Wener,Alexander L. Greninger,Meei Li Huang,Keith R. Jerome,Anna Wald,Connie Celum,Helen Y. Chu,Jared M. Baeten +29 more
TL;DR: This randomized controlled trial tests hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection.
Posted ContentDOI
Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area
Scott Wesley Long,Randall J. Olsen,Paul A. Christensen,David W. Bernard,James J. Davis,Maulik Shukla,Marcus Nguyen,Matthew Ojeda Saavedra,Prasanti Yerramilli,Layne Pruitt,Sishir Subedi,Hung-Che Kuo,Heather Hendrickson,Ghazaleh Eskandari,Hoang A. T. Nguyen,James Hunter Long,Muthiah Kumaraswami,Jule Goike,Daniel R. Boutz,Jimmy Gollihar,Jason S. McLellan,Chia-Wei Chou,Kamyab Javanmardi,Ilya J. Finkelstein,James M. Musser +24 more
TL;DR: This study is the first analysis of the molecular architecture of SARS-CoV-2 in two infection waves in a major metropolitan region, and exploited the genomic data to generate defined single amino acid replacements in the receptor binding domain of spike protein that produced decreased recognition by the neutralizing monoclonal antibody CR30022.
Journal ArticleDOI
Potent and protective IGHV3-53/3-66 public antibodies and their shared escape mutant on the spike of SARS-CoV-2.
Qi Zhang,Bin Ju,Jiwan Ge,Jasper Fuk-Woo Chan,Jasper Fuk-Woo Chan,Lin Cheng,Ruoke Wang,Weijin Huang,Mengqi Fang,Peng Chen,Bing Zhou,Shuo Song,Sisi Shan,Baohua Yan,Senyan Zhang,Xiangyang Ge,Jiazhen Yu,Juanjuan Zhao,Haiyan Wang,Li Liu,Qining Lv,Lili Fu,Xuanling Shi,Kwok-Yung Yuen,Kwok-Yung Yuen,Lei Liu,Youchun Wang,Zhiwei Chen,Zhiwei Chen,Linqi Zhang,Xinquan Wang,Zheng Zhang +31 more
TL;DR: In this article, a total of 165 antibodies from eight SARS-CoV-19 patients were examined and found that potent nAbs from different patients have disproportionally high representation of IGHV3-53/3-66 usage, and therefore termed as public antibodies.
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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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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