Surface-modified protein nanospheres as potential antiviral agents.

A novel application of surface-modified protein nanospheres as potential antiviral agents is illustrated. By using a single-step sonochemical process, bovine serum albumin nanospheres were generated, whose surface was covalently conjugated with mercaptoethane sulfonate to chemically and electrostatically mimic cellular heparan sulfate. The nanospheres effectively inhibited HSV-1 infection.

Inhibition of HSV-1 attachment, entry, and cell-to-cell spread by functionalized multivalent gold nanoparticles.

The use of modified nanoparticles in interactions with biological targets is attracting rapidly increasing attention. In this Full Paper, the application of gold nanoparticles capped with mercaptoethanesulfonate (Au-MES NPs) as effective inhibitors of Herpes simplex virus type 1 infection based on their ability to mimic cell-surface-receptor heparan sulfate is described. Mechanistic studies reveal that Au-MES NPs interfere with viral attachment, entry, and cell-to-cell spread, thereby preventing subsequent viral infection in a multimodal manner. The ligand multiplicity achieved with carrier nanoparticles is crucial in generating polyvalent interactions with the virus at high specificity, strength, and efficiency. Such multivalent-nanoparticle-mediated inhibition is a promising approach for alternative antiviral therapy.

Inhibition of herpes simplex virus type 1 infection by silver nanoparticles capped with mercaptoethane sulfonate.

Interactions between biomolecules and nanoparticles suggest the use of nanoparticles for various medical interventions. The attachment and entry of herpes simplex virus type 1 (HSV-1) into cells involve interaction between viral envelope glycoproteins and cell surface heparan sulfate (HS). Based on this mechanism, we designed silver nanoparticles that are capped with mercaptoethane sulfonate (Ag-MES). These nanoparticles are predicted to target the virus and to compete for its binding to cellular HS through their sulfonate end groups, leading to the blockage of viral entry into the cell and to the prevention of subsequent infection. Structurally defined Ag-MES nanoparticles that are readily redispersible in water were sonochemically synthesized. No toxic effects of these nanoparticles on host cells were observed. Effective inhibition of HSV-1 infection in cell culture by the capped nanoparticles was demonstrated. However, application of the soluble surfactant MES failed to inhibit viral infection, implying that the antiviral effect of Ag-MES nanoparticles is imparted by their multivalent nature and spatially directed MES on the surface. Our results suggest that capped nanoparticles may serve as useful topical agents for the prevention of infections with pathogens dependent on HS for entry.