Humanized COVID‐19 decoy antibody effectively blocks viral entry and prevents SARS‐CoV‐2 infection

Autor: Kuo‐Yen Huang, Ming‐Shiu Lin, Ting‐Chun Kuo, Ci‐Ling Chen, Chung‐Chih Lin, Yu‐Chi Chou, Tai‐Ling Chao, Yu‐Hao Pang, Han‐Chieh Kao, Rih‐Sheng Huang, Steven Lin, Sui‐Yuan Chang, Pan‐Chyr Yang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 13, Iss 1, Pp 1-19 (2020)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.202012828
Popis: 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.
Databáze: Directory of Open Access Journals
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