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...
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Public Library of Science (PLoS)
2021
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oai:doaj.org-article:3eeea7e74b56462fa7c2d9a473c804ec2021-12-02T19:59:42ZStructure-guided antibody cocktail for prevention and treatment of COVID-19.1553-73661553-737410.1371/journal.ppat.1009704https://doaj.org/article/3eeea7e74b56462fa7c2d9a473c804ec2021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009704https://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.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, p e1009704 (2021) |
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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. |
| 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/3eeea7e74b56462fa7c2d9a473c804ec |
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