Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection
Journal
EMBO Molecular Medicine
Journal Volume
13
Journal Issue
1
Pages
e12828
Date Issued
2021
Author(s)
Huang, Kuo-Yen
Lin, Ming-Shiu
Kuo, Ting-Chun
Chen, Ci-Ling
Lin, Chung-Chih
Chou, Yu-Chi
Pang, Yu-Hao
Kao, Han-Chieh
Huang, Rih-Sheng
Lin, Steven
Abstract
To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a humanized decoy antibody (ACE2-Fc fusion protein) was designed to target the interaction between viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2). First, we demonstrated that ACE2-Fc could specifically abrogate virus replication by blocking the entry of SARS-CoV-2 spike-expressing pseudotyped virus into both ACE2-expressing lung cells and lung organoids. The impairment of viral entry was not affected by virus variants, since efficient inhibition was also observed in six SARS-CoV-2 clinical strains, including the D614G variants which have been shown to exhibit increased infectivity. The preservation of peptidase activity also enables ACE2-Fc to reduce the angiotensin II-mediated cytokine cascade. Furthermore, this Fc domain of ACE2-Fc was shown to activate NK cell degranulation after co-incubation with Spike-expressing H1975 cells. These promising characteristics potentiate the therapeutic prospects of ACE2-Fc as an effective treatment for COVID-19.
SDGs
Publisher
Blackwell Publishing Ltd
Type
journal article