Multivalent Peptide-Nanoparticle Conjugates for Influenza-Virus Inhibition.

To inhibit binding of the influenza A virus to the host cell glycocalyx, we generate multivalent peptide-polymer nanoparticles binding with nanomolar affinity to the virus via its spike protein hemagglutinin. The chosen dendritic polyglycerol scaffolds are highly biocompatible and well suited for a multivalent presentation. We could demonstrate in vitro that by increasing the size of the polymer scaffold and adjusting the peptide density, viral infection is drastically reduced. Such a peptide-polymer conjugate qualified also in an in vivo infection scenario. With this study we introduce the first non-carbohydrate-based, covalently linked, multivalent virus inhibitor in the nano- to picomolar range by ensuring low peptide-ligand density on a larger dendritic scaffold.