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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A potential SARS-CoV-2 variant of interest (VOI) harboring mutation E484K in the Spike protein was identified within lineage B.1.1.33 circulating in Brazil
Paola Cristina Resende,Tiago Gräf,Anna Carolina Dias Paixão,Luciana Appolinario,Renata Serrano Lopes,Ana Carolina da Fonseca Mendonça,Alice Sampaio Barreto da Rocha,Fernando Couto Motta,Lidio Gonçalves Lima Neto,Ricardo Khouri,Pedro Santos-Muccillo,João Felipe Bezerra,Dalane Loudal Florentino Teixeira,Irina Nastassja Riediger,Maria do Carmo Debur,Rodrigo Ribeiro-Rodrigues,Anderson Brandao Leite,Cliomar Alves do Santos,Tatiana Schäffer Gregianini,Sandra Fernandes,A Bernardes,Andrea Cony Cavalcanti,Fabio Miyajima,Claudio Sachhi,Tirza Mattos,Cristiano Fernandes da Costa,Edson Delatorre,Gabriel Luz Wallau,Felipe Gomes Naveca,Gonzalo Bello,Marilda M. Siqueira +30 more
TL;DR: In this article, the authors reported the identification of a new SARS-CoV-2 VOI within lineage B.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021.
Posted ContentDOI
Linear epitope landscape of SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients
Yang Li,Ming-liang Ma,Qing Lei,Feng Wang,Dan-yun Lai,Hongyan Hou,Zhaowei Xu,Bo Zhang,Hong Chen,Caizheng Yu,Jun-biao Xue,Yun-xiao Zheng,Xue-ning Wang,He-wei Jiang,Hai-nan Zhang,Huan Qi,Shu-Juan Guo,Yandi Zhang,Xiaosong Lin,Zongjie Yao,Jiaoxiang Wu,Huiming Sheng,Ziyong Sun,Xionglin Fan,Sheng-Ce Tao +24 more
TL;DR: Wang et al. as mentioned in this paper generated a linear epitope landscape of Spike protein by analyzing serum IgG response of 1,051 COVID-19 patients with a peptide microarray, revealing two regions that rich of linear epitopes, i.e., CTD and a region close to the S29 cleavage site and fusion peptide.
Posted ContentDOI
Structures of potent and convergent neutralizing antibodies bound to the SARS-CoV-2 spike unveil a unique epitope responsible for exceptional potency
Shuo Du,Y Cao,Qinyu Zhu,Guopeng Wang,Xiao-Xia Du,Runsheng He,Hua Xu,Yinghui Zheng,Bo Wang,Yali Bai,Chenggong Ji,Ayijiang Yisimayi,Qisheng Wang,Ning Gao,Sunney Xie,Xiao-Dong Su,Junyu Xiao +16 more
TL;DR: The results rationalize a unique epitope that leads to exceptional neutralization potency, and provide guidance for NAb therapeutics and vaccine designs against SARS-CoV-2.
Journal ArticleDOI
Synthetic Neutralizing Peptides Inhibit the Host Cell Binding of Spike Protein and Block Infection of SARS-CoV-2.
Tao Wang,Xiaocui Fang,Tao Wen,Jian Liu,Zhaoyi Zhai,Zhaoyi Zhai,Zhiyou Wang,Jie Meng,Yanlian Yang,Yanlian Yang,Chen Wang,Chen Wang,Haiyan Xu +12 more
TL;DR: In this article, three chemically synthetic neutralizing peptides were obtained via quartz crystal microbalance measurement screening, which showed high affinity at nanomole to the S1 subunit of the spike protein and wild-type SARS-CoV-2 pseudovirus.
Journal ArticleDOI
An update on COVID-19: SARS-CoV-2 variants, antiviral drugs, and vaccines
TL;DR: A comprehensive review of the dynamic nature of SARS-CoV-2 transmission is presented in this paper , which summarizes the virus transmission, variants (a variant of concern and a variant of interest), antiviral drugs and vaccines utilized against SARS CoV2 at a glance.
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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Davide F. Robbiani,Davide F. Robbiani,Christian Gaebler,Frauke Muecksch,Julio C. C. Lorenzi,Zijun Wang,Alice Cho,Marianna Agudelo,Christopher O. Barnes,Anna Gazumyan,Shlomo Finkin,Thomas Hagglof,Thiago Y. Oliveira,Charlotte Viant,Arlene Hurley,Hans Heinrich Hoffmann,Katrina G. Millard,Rhonda G. Kost,Melissa Cipolla,Kristie Gordon,Filippo Bianchini,Spencer T. Chen,Victor A. Ramos,Roshni Patel,Juan Dizon,Irina Shimeliovich,Pilar Mendoza,Harald Hartweger,Lilian Nogueira,Maggi Pack,Jill Horowitz,Fabian Schmidt,Yiska Weisblum,Eleftherios Michailidis,Alison W. Ashbrook,Eric Waltari,John E. Pak,Kathryn E. Huey-Tubman,Nicholas Koranda,Pauline R. Hoffman,Anthony P. West,Charles M. Rice,Theodora Hatziioannou,Pamela J. Bjorkman,Paul D. Bieniasz,Paul D. Bieniasz,Marina Caskey,Michel C. Nussenzweig,Michel C. Nussenzweig +48 more
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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