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

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

Author Information

EMBO Mol Med (2020)0:e12828https://doi.org/10.15252/emmm.202012828

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.15252/emmm.202012828

PDF: https://www.embopress.org/doi/epdf/10.15252/emmm.202012828

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 coincubation with Spike‐expressing H1975 cells. These promising characteristics potentiate the therapeutic prospects of ACE2‐Fc as an effective treatment for COVID‐19.

https://www.embopress.org/doi/abs/10.15252/emmm.202012828