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

• Published in: The Journal of infectious diseases Vol. 228; no. 12; pp. 1675 - 1679
• Main Authors: Chêne, Arnaud, Desrames, Alexandra, Tomlinson, Alice, Ruffié, Claude, Tangy, Frédéric, Gamain, Benoît
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 20-12-2023
• Subjects: Angiotensin-Converting Enzyme 2 - metabolism; Antibodies, Viral; COVID-19; Epstein-Barr Virus Infections; Herpesvirus 4, Human - genetics; Humans; Life Sciences; Peptidyl-Dipeptidase A - genetics; Protein Binding; Recombinant Proteins - metabolism; SARS-CoV-2; Spike Glycoprotein, Coronavirus; COVID-19; soluble ACE2; SARS-CoV-2; BMFP; Epstein-Barr virus
• ISSN: 0022-1899; 1537-6613
• 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.
A soluble form of recombinant angiotensin-converting enzyme 2—fused to an Epstein-Barr virus antigen enabling the reorientation of a preexisting humoral response toward Epstein-Barr virus against SARS-CoV-2 particles—showed therapeutic potential to universally block coronavirus cell entry and clear viral particles.