An ACE2-Based Bimodular Fusion Protein Enables Reorientation of Endogenous Anti-Epstein-Barr Virus Antibodies Toward SARS-CoV-2 Spike

J Infect Dis. 2023 Dec 20;228(12):1675-1679. doi: 10.1093/infdis/jiad329.

Abstract

The use of soluble recombinant angiotensin-converting enzyme 2 (rACE2) as a decoy capable of blocking SARS-CoV-2 entry into cells has been envisaged as a therapeutic strategy to reduce viral loads in patients with severe COVID-19. We engineered a novel form of rACE2, fused to the Epstein-Barr virus antigen P18F3 (rACE2-P18F3), to reorient a preexisting humoral response toward Epstein-Barr virus against SARS-CoV-2 particles. Recombinant ACE2-P18F3 was able to bind to the SARS-CoV-2 spike protein, neutralize viral entry into cells, and promote the phagocytosis of spheres coated with different spike variants by monocytic cells. The results position rACE2-P18F3 as a promising therapeutic candidate to universally block coronavirus cell entry and clear viral particles.

Trial registration: ClinicalTrials.gov NCT04335136.

Keywords: BMFP; COVID-19; Epstein-Barr virus; SARS-CoV-2; soluble ACE2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2* / metabolism
  • Antibodies, Viral* / immunology
  • COVID-19*
  • Herpesvirus 4, Human* / immunology
  • Humans
  • Peptidyl-Dipeptidase A / genetics
  • Protein Binding
  • Recombinant Proteins / metabolism
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus* / immunology

Substances

  • Angiotensin-Converting Enzyme 2
  • Antibodies, Viral
  • Peptidyl-Dipeptidase A
  • Recombinant Proteins
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Associated data

  • ClinicalTrials.gov/NCT04335136