CORONA - ViKon - Targeted elimination of SARS-CoV-2 by microparticle-based high-affinity Visrus binding conjugates; subproject 3: Functional testing of binding, neutralization and phagocytosis induction of SARS-CoV2-binding microparticles.

The interaction of the surface protein (spike protein) of SARS-CoV-2 with the angiotensin-converting enzyme 2 (ACE2) of human cells mediates the uptake of virus particles into the cell interior and thus forms the starting point of infection. Due to its small size, elimination of SARS-CoV-2 by phagocytosis is not normally possible. However, phagocytosis can be exploited to eliminate viruses. This requires that viruses are bound to sufficiently large aggregates (> 400 nm) that can be recognized and rendered harmless by immune effector cells such as macrophages. In this project, ACE2 receptor peptide analogs will be tailored to couple to microparticles to provide a therapeutically effective competitor to surface fixation of viruses to human cells. By coupling the host cell receptor domain to microparticles, on the one hand, the uptake of SARS-CoV-2 into the host cell should be competitively prevented and, on the other hand, the targeted destruction of these aggregates by phagocytosis should be promoted. In this subproject, the ACE2-functionalized nanoparticles will be characterized with respect to their interaction with viral particles and macrophages. Experimental systems will be established to investigate the essential steps of the proposed mechanism of action: 1) the binding of the particles to the viral spike protein, 2) the ability to stop infection by direct interaction between viral particles and the cellular ACE2 uptake receptor ("neutralization"), and 3) the ability to induce their phagocytosis and elimination by cells of the immune system after binding of viruses. The aim is to perform a range of functional assays within a broadly available safety level (S2) by using so-called pseudoviruses, allowing optimization of peptide-loaded particles in terms of binding affinity and phagocytosis induction.