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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Coronavirus 2019 Infectious Disease Epidemic: Where We Are, What Can Be Done and Hope For.
Michele Carbone,Michele Carbone,John A. Lednicky,Shu-Yuan Xiao,Mario Venditti,Enrico M. Bucci +5 more
TL;DR: In this article, the authors discuss the issues related to disseminating accurate information, physicians, health professionals, and scientists play a key role in addressing myths and anxiety, help public health officials enact measures to decrease infections, and provide the best care for those who become sick.
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Plasmablast-derived antibody response to acute SARS-CoV-2 infection in humans
Kuan-Ying A. Huang,Tiong Kit Tan,Ting-Hua Chen,Chung-Guei Huang,Chung-Guei Huang,Ruth Harvey,Saira Hussain,Cheng-Pin Chen,Adam Harding,Javier Gilbert-Jaramillo,Xu Liu,Michael L. Knight,Lisa Schimanski,Lisa Schimanski,Shin-Ru Shih,Shin-Ru Shih,Yi-Chun Lin,Chien-Yu Cheng,Shu-Hsing Cheng,Yhu-Chering Huang,Tzou Yien Lin,Rolle Rahikainen,Mark Howarth,Jia-Tsrong Jan,Che Ma,William James,Rodney S. Daniels,John W. McCauley,Pramila Rijal,Pramila Rijal,Alain Townsend,Alain Townsend +31 more
TL;DR: The cross-reactive plasmablast-derived antibodies harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection, and non-competing pairs of neutralising antibodies were identified, which offer potential templates for the development of prophylactic and therapeutic agents against SARS.
Journal ArticleDOI
Neutralizing antibodies against SARS-CoV-2: current understanding, challenge and perspective
TL;DR: In this article, the authors provide a systemic overview of SARS-CoV-2 specific or cross-reactive neutralizing antibodies and discuss their structures, functions and neutralization mechanisms.
Posted ContentDOI
SARS-CoV-2 Omicron spike H655Y mutation is responsible for enhancement of the endosomal entry pathway and reduction of cell surface entry pathways
TL;DR: Protease inhibitors are used to block each viral entry pathway mediated by the three host proteases (cathepsin B/L, TMPRSS2, and metalloproteinases) in various cell types to suggest that Omicron has altered entry properties and fusogenicity, leading to modulations of tissue and cell tropism, and reduced pathogenicity.
Journal ArticleDOI
Clinical Management of COVID-19: A Review of Pharmacological Treatment Options
TL;DR: An updated review of pharmacological agents that have been developed and/or repurposed for the treatment of COVID-19 is provided, showing mixed data on efficacy and safety of the currently utilized drugs.
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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