Inhibition of influenza virus infection by multivalent sialic-acid- functionalized gold nanoparticles

Abstract

An efficient synthesis of sialic-acid-terminated glycerol dendron to chemically functionalize 2 nm and 14 nm gold nanoparticles (AuNPs) is described. These nanoparticles are highly stable and show high activity towards the inhibition of influenza virus infection. As the binding of the viral fusion protein hemagglutinin to the host cell surface is mediated by sialic acid receptors, a multivalent interaction with sialic-acid-functionalized AuNPs is expected to competitively inhibit viral infection. Electron microscopy techniques and biochemical analysis show a high binding affinity of the 14 nm AuNPs to hemagglutinin on the virus surface and, less efficiently, to isolated hemagglutinin. The functionalized AuNPs are nontoxic to the cells under the conditions studied. This approach allows a new type of molecular-imaging activity-correlation and is of particular relevance for further application in alternative antiviral therapy. Densely sugar-coated gold nanoparticles are prepared by covalently attaching sialic-acid-modified dendrons to the nanoparticle surface. Such multivalent constructs are designed to bind hemagglutinin envelope-protein arrays on the influenza surface, thus inhibiting viral invasion of host cells. Various chemical and biological assays, as well as electron microscopy, are presented to validate this approach and visualize for the first time the multiple binding of AuNP inhibitors to the virus surface. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.