20201106 Lin S Epub

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

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

EMBO Mol Med. 2021 Jan 11; 13(1):e12828.
doi: 10.15252/emmm.202012828

閱讀文章

Huang KY, Lin MS, Kuo TC, Chen CL, Lin CC, Chou YC, Chao TL, Pang YH, Kao HC, Huang RS, Lin S, Chang SY, Yang PC

摘要

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.