Open AccessStructure-guided antibody cocktail for prevention and treatment of COVID-19
Author(s) -
Shih-Chieh Su,
Tzu-Jing Yang,
Pei-Yu Yu,
Kang-Hao Liang,
WanYu Chen,
Chun-Wei Yang,
Hsiu-Ting Lin,
Mei-Jung Wang,
RueiMin Lu,
Hsien-Cheng Tso,
Meng-Jhe Chung,
Tzung-Yang Hsieh,
YuLing Chang,
Shin-Chang Lin,
FangYu Hsu,
Feng-Yi Ke,
YiHsuan Wu,
Yu-Chyi Hwang,
I-Ju Liu,
Jian-Jong Liang,
Chun-Che Liao,
Hui-Ying Ko,
ChengPu Sun,
Ping-Yi Wu,
Jia-Tsrong Jan,
Yuan-Chih Chang,
Yi-Ling Lin,
MiHua Tao,
ShangTe Danny Hsu,
HanChung Wu
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009704
Subject(s) - antibody , virology , epitope , neutralization , in vivo , coronavirus , biology , immunity , immune system , neutralizing antibody , immunology , virus , covid-19 , medicine , disease , infectious disease (medical specialty) , microbiology and biotechnology , pathology
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.