Structure-guided antibody cocktail for prevention and treatment of COVID-19

Development of effective therapeutics for mitigating the COVID-19 pandemic is a pressing global need. Neutralizing antibodies are known to be effective antivirals, as they can be rapidly deployed to prevent disease progression and can accelerate patient recovery without the need for fully developed...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shih-Chieh Su, Tzu-Jing Yang, Pei-Yu Yu, Kang-Hao Liang, Wan-Yu Chen, Chun-Wei Yang, Hsiu-Ting Lin, Mei-Jung Wang, Ruei-Min Lu, Hsien-Cheng Tso, Meng-Jhe Chung, Tzung-Yang Hsieh, Yu-Ling Chang, Shin-Chang Lin, Fang-Yu Hsu, Feng-Yi Ke, Yi-Hsuan Wu, Yu-Chyi Hwang, I-Ju Liu, Jian-Jong Liang, Chun-Che Liao, Hui-Ying Ko, Cheng-Pu Sun, Ping-Yi Wu, Jia-Tsrong Jan, Yuan-Chih Chang, Yi-Ling Lin, Mi-Hua Tao, Shang-Te Danny Hsu, Han-Chung Wu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/16354bc5faef45df8f05181199b75656
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:16354bc5faef45df8f05181199b75656
record_format	dspace
spelling	oai:doaj.org-article:16354bc5faef45df8f05181199b756562021-11-04T05:51:24ZStructure-guided antibody cocktail for prevention and treatment of COVID-191553-73661553-7374https://doaj.org/article/16354bc5faef45df8f05181199b756562021-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530329/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Development of effective therapeutics for mitigating the COVID-19 pandemic is a pressing global need. Neutralizing antibodies are known to be effective antivirals, as they can be rapidly deployed to prevent disease progression and can accelerate patient recovery without the need for fully developed host immunity. Here, we report the generation and characterization of a series of chimeric antibodies against the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Some of these antibodies exhibit exceptionally potent neutralization activities in vitro and in vivo, and the most potent of our antibodies target three distinct non-overlapping epitopes within the RBD. Cryo-electron microscopy analyses of two highly potent antibodies in complex with the SARS-CoV-2 spike protein suggested they may be particularly useful when combined in a cocktail therapy. The efficacy of this antibody cocktail was confirmed in SARS-CoV-2-infected mouse and hamster models as prophylactic and post-infection treatments. With the emergence of more contagious variants of SARS-CoV-2, cocktail antibody therapies hold great promise to control disease and prevent drug resistance. Author summary Effective approaches to mitigate the COVID-19 pandemic are a pressing global need. One promising strategy is to combine neutralizing antibodies that can reduce viral load to prevent disease progression and accelerate patient recovery. However, the current supply of therapeutic antibodies for COVID-19 is insufficient to fill the enormous demand, and escape mutants may compromise the utility of existing drugs. Thus, there is an urgent worldwide need to develop highly potent neutralizing antibody cocktails. We generated a series of chimeric antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein, which potently neutralize authentic SARS-CoV-2 infection according to the plaque reduction neutralization test (PRNT) and pseudovirus-based inhibition assay. These antibodies can be classified into three distinct groups based on their targets within the receptor-binding motif. Cryo-electron microscopy structural analyses of two representative receptor-binding domain-chimeric antibodies in complex with the SARS-CoV-2 spike protein further revealed two sets of non-overlapping epitopes, suggesting the potential for their combination in a therapeutic antibody cocktail. The prophylactic and therapeutic effects of these antibodies and their combination were demonstrated in SARS-CoV-2-infected mouse and hamster models. Thus, our potent neutralizing antibody cocktail has strong potential for development as an effective therapeutic drug to prevent and treat SARS-CoV-2 infection.Shih-Chieh SuTzu-Jing YangPei-Yu YuKang-Hao LiangWan-Yu ChenChun-Wei YangHsiu-Ting LinMei-Jung WangRuei-Min LuHsien-Cheng TsoMeng-Jhe ChungTzung-Yang HsiehYu-Ling ChangShin-Chang LinFang-Yu HsuFeng-Yi KeYi-Hsuan WuYu-Chyi HwangI-Ju LiuJian-Jong LiangChun-Che LiaoHui-Ying KoCheng-Pu SunPing-Yi WuJia-Tsrong JanYuan-Chih ChangYi-Ling LinMi-Hua TaoShang-Te Danny HsuHan-Chung WuPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Shih-Chieh Su Tzu-Jing Yang Pei-Yu Yu Kang-Hao Liang Wan-Yu Chen Chun-Wei Yang Hsiu-Ting Lin Mei-Jung Wang Ruei-Min Lu Hsien-Cheng Tso Meng-Jhe Chung Tzung-Yang Hsieh Yu-Ling Chang Shin-Chang Lin Fang-Yu Hsu Feng-Yi Ke Yi-Hsuan Wu Yu-Chyi Hwang I-Ju Liu Jian-Jong Liang Chun-Che Liao Hui-Ying Ko Cheng-Pu Sun Ping-Yi Wu Jia-Tsrong Jan Yuan-Chih Chang Yi-Ling Lin Mi-Hua Tao Shang-Te Danny Hsu Han-Chung Wu Structure-guided antibody cocktail for prevention and treatment of COVID-19
description	Development of effective therapeutics for mitigating the COVID-19 pandemic is a pressing global need. Neutralizing antibodies are known to be effective antivirals, as they can be rapidly deployed to prevent disease progression and can accelerate patient recovery without the need for fully developed host immunity. Here, we report the generation and characterization of a series of chimeric antibodies against the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Some of these antibodies exhibit exceptionally potent neutralization activities in vitro and in vivo, and the most potent of our antibodies target three distinct non-overlapping epitopes within the RBD. Cryo-electron microscopy analyses of two highly potent antibodies in complex with the SARS-CoV-2 spike protein suggested they may be particularly useful when combined in a cocktail therapy. The efficacy of this antibody cocktail was confirmed in SARS-CoV-2-infected mouse and hamster models as prophylactic and post-infection treatments. With the emergence of more contagious variants of SARS-CoV-2, cocktail antibody therapies hold great promise to control disease and prevent drug resistance. Author summary Effective approaches to mitigate the COVID-19 pandemic are a pressing global need. One promising strategy is to combine neutralizing antibodies that can reduce viral load to prevent disease progression and accelerate patient recovery. However, the current supply of therapeutic antibodies for COVID-19 is insufficient to fill the enormous demand, and escape mutants may compromise the utility of existing drugs. Thus, there is an urgent worldwide need to develop highly potent neutralizing antibody cocktails. We generated a series of chimeric antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein, which potently neutralize authentic SARS-CoV-2 infection according to the plaque reduction neutralization test (PRNT) and pseudovirus-based inhibition assay. These antibodies can be classified into three distinct groups based on their targets within the receptor-binding motif. Cryo-electron microscopy structural analyses of two representative receptor-binding domain-chimeric antibodies in complex with the SARS-CoV-2 spike protein further revealed two sets of non-overlapping epitopes, suggesting the potential for their combination in a therapeutic antibody cocktail. The prophylactic and therapeutic effects of these antibodies and their combination were demonstrated in SARS-CoV-2-infected mouse and hamster models. Thus, our potent neutralizing antibody cocktail has strong potential for development as an effective therapeutic drug to prevent and treat SARS-CoV-2 infection.
format	article
author	Shih-Chieh Su Tzu-Jing Yang Pei-Yu Yu Kang-Hao Liang Wan-Yu Chen Chun-Wei Yang Hsiu-Ting Lin Mei-Jung Wang Ruei-Min Lu Hsien-Cheng Tso Meng-Jhe Chung Tzung-Yang Hsieh Yu-Ling Chang Shin-Chang Lin Fang-Yu Hsu Feng-Yi Ke Yi-Hsuan Wu Yu-Chyi Hwang I-Ju Liu Jian-Jong Liang Chun-Che Liao Hui-Ying Ko Cheng-Pu Sun Ping-Yi Wu Jia-Tsrong Jan Yuan-Chih Chang Yi-Ling Lin Mi-Hua Tao Shang-Te Danny Hsu Han-Chung Wu
author_facet	Shih-Chieh Su Tzu-Jing Yang Pei-Yu Yu Kang-Hao Liang Wan-Yu Chen Chun-Wei Yang Hsiu-Ting Lin Mei-Jung Wang Ruei-Min Lu Hsien-Cheng Tso Meng-Jhe Chung Tzung-Yang Hsieh Yu-Ling Chang Shin-Chang Lin Fang-Yu Hsu Feng-Yi Ke Yi-Hsuan Wu Yu-Chyi Hwang I-Ju Liu Jian-Jong Liang Chun-Che Liao Hui-Ying Ko Cheng-Pu Sun Ping-Yi Wu Jia-Tsrong Jan Yuan-Chih Chang Yi-Ling Lin Mi-Hua Tao Shang-Te Danny Hsu Han-Chung Wu
author_sort	Shih-Chieh Su
title	Structure-guided antibody cocktail for prevention and treatment of COVID-19
title_short	Structure-guided antibody cocktail for prevention and treatment of COVID-19
title_full	Structure-guided antibody cocktail for prevention and treatment of COVID-19
title_fullStr	Structure-guided antibody cocktail for prevention and treatment of COVID-19
title_full_unstemmed	Structure-guided antibody cocktail for prevention and treatment of COVID-19
title_sort	structure-guided antibody cocktail for prevention and treatment of covid-19
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/16354bc5faef45df8f05181199b75656
work_keys_str_mv	AT shihchiehsu structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT tzujingyang structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT peiyuyu structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT kanghaoliang structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT wanyuchen structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT chunweiyang structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT hsiutinglin structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT meijungwang structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT rueiminlu structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT hsienchengtso structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT mengjhechung structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT tzungyanghsieh structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT yulingchang structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT shinchanglin structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT fangyuhsu structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT fengyike structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT yihsuanwu structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT yuchyihwang structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT ijuliu structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT jianjongliang structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT chuncheliao structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT huiyingko structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT chengpusun structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT pingyiwu structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT jiatsrongjan structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT yuanchihchang structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT yilinglin structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT mihuatao structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT shangtedannyhsu structureguidedantibodycocktailforpreventionandtreatmentofcovid19 AT hanchungwu structureguidedantibodycocktailforpreventionandtreatmentofcovid19
_version_	1718445193570549760

Structure-guided antibody cocktail for prevention and treatment of COVID-19

Ejemplares similares