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.

Multivalent Peptide–Nanoparticle Conjugates for Influenza‐Virus Inhibition

“…High molecular‐weight scaffolds displaying a large number of low affinity SA derived ligands were used to achieve high HA avidity. Over the years several carrier systems were employed as scaffolds ranging from polymers,6, 8, 9 dendrimers,10, 11, 12, 13 liposomes,5, 14 proteins,15 to gold nanoparticles 16. The most affine binders reported to date consist of SA tethered to linear polyacrylamide polymers 6.…”

Nanoparticle-cored dendrimers: functional hybrid nanocomposites as a new platform for drug delivery systems

“…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-acidfunctionalized NPs is expected to competitively inhibit viral infection. 89 The diverse functional possibilities of NCDs allows for a variety of approaches for nanocarriers design (see Figure 4). Fox et al reported the synthesis of water soluble Au NCDs that exhibit micellar properties capable of encapsulating pinacyanol chloride.…”

Multivalenz als chemisches Organisations‐ und Wirkprinzip

“…Bindung von Viruspartikeln an Nanopartikeln [80,81] Fluoreszenzmikroskopie Fluoreszenzintensität als Funktion der Zeit Geschwindigkeitskonstante Bindung von CdS-Quantenpunkten mit variabler Ligandenmultivalenz an GABA(C)-Rezeptoren auf einer Zellmembran [82] dynamische Lichtstreuung (DLS) hydrodynamischer Durchmesser (aus zeitlicher ¾nderung der Streuintensität) als Funktion der Zeit Aggregationsgeschwindigkeitskonstante (Maß für Stabilität gegen Aggregation infolge multivalenter Stabilisierung…”