Open AccessHumanized COVID‐19 decoy antibody effectively blocks viral entry and prevents SARS‐CoV‐2 infection
Author(s) -
Huang KuoYen,
Lin MingShiu,
Kuo TingChun,
Chen CiLing,
Lin ChungChih,
Chou YuChi,
Chao TaiLing,
Pang YuHao,
Kao HanChieh,
Huang RihSheng,
Lin Steven,
Chang SuiYuan,
Yang PanChyr
Publication year - 2020
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202012828
Subject(s) - covid-19 , library science , chinese academy of sciences , medicine , political science , china , infectious disease (medical specialty) , law , disease , computer science
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.