20211021 Hsu STD paper photo

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

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

PLOS PATHOGENS. 2021 Oct 21; 17(10), e1009704.
doi: 10.1371/journal.ppat.1009704


Su SC, Yang TJ, Yu PY, Liang KH, Chen WY, Yang CW, Lin HT, Wang MJ, Lu RM, Tso HC, Chung MJ, Hsieh TY, Chang YL, Lin SC, Hsu FY, Ke FY, Wu YH, Hwang YC, Liu IJ, Liang JJ, Liao CC, Ko HY, Sun CP, Wu PY, Jan JT, Chang YC, Lin YL*, Tao MH*, Hsu STD*, Wu HC*


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.