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. Epub 2020 Nov 30.


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.

Keywords: ACE2-Fc; COVID-19; SARS-CoV-2; decoy antibody; virus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / immunology
  • Animals
  • Antibodies, Monoclonal, Humanized / immunology
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibodies, Viral / immunology
  • Antibodies, Viral / pharmacology*
  • COVID-19 / immunology
  • COVID-19 / prevention & control*
  • Chlorocebus aethiops
  • HEK293 Cells
  • Host-Pathogen Interactions / drug effects
  • Humans
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / pharmacology
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / physiology
  • Spike Glycoprotein, Coronavirus / immunology*
  • Vero Cells
  • Virus Internalization / drug effects*


  • Antibodies, Monoclonal, Humanized
  • Antibodies, Viral
  • Recombinant Fusion Proteins
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2