An ACE2-based bimodular fusion protein enables reorientation of endogenous anti-Epstein-Barr virus antibodies towards SARS-CoV-2 Spike.

The use of soluble recombinant ACE2 (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 suffering from severe COVID-19. We engineered a novel form of rACE2, fused to the Epstein-Barr virus (EBV) antigen P18F3 (rACE2-P18F3), to reorient a pre-existing humoral response towards EBV against SARS-CoV-2 particles. Recombinant ACE2-P18F3 was able to bind to the SARS-CoV-2 spike protein, neutralized viral entry into cells and promoted 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 coronaviruses cell entry and clear viral particles.