Adaptive Flexible Sialylated Nanogels as Highly Potent Influenza A Virus Inhibitors
Sumati Bhatia, Malte Hilsch, Jose Luis Cuellar‐Camacho, Kai Ludwig, Chuanxiong Nie, Badri Parshad, Matthias Wallert, Stephan Block, Daniel Lauster, Christoph Böttcher, Andreas Herrmann, Rainer Haag
Abstract
Abstract Flexible multivalent 3D nanosystems that can deform and adapt onto the virus surface via specific ligand–receptor multivalent interactions can efficiently block virus adhesion onto the cell. We here report on the synthesis of a 250 nm sized flexible sialylated nanogel that adapts onto the influenza A virus (IAV) surface via multivalent binding of its sialic acid (SA) residues with hemagglutinin spike proteins on the virus surface. We could demonstrate that the high flexibility of sialylated nanogel improves IAV inhibition by 400 times as compared to a rigid sialylated nanogel in the hemagglutination inhibition assay. The flexible sialylated nanogel efficiently inhibits the influenza A/X31 (H3N2) infection with IC 50 values in low picomolar concentrations and also blocks the virus entry into MDCK‐II cells.