Histidine- and glycine-functionalized cerium oxide nanoparticles: Physicochemical properties and antiviral activity

Cerium oxide nanoparticles (CeNPs) show great promise in biomedical applications such as theranostics of various diseases, including viral infection. In this work, we synthesized bare, histidine-and glycinefunctionalized CeNPs sols and characterized them using DLS, TEM and AFM imaging, synchrotron radiation based techniques (XPS, RPES, NEXAFS). Toxicity and antiviral activity of CeNPs were evaluated using two cell lines (mouse fibroblasts L929 and monkey kidney epithelial cells MA-104) and three types of enveloped viruses (vesicular stomatitis virus VSV, bovine beta coronavirus BCoV-1 and herpes simplex virus HSV-1/2) in vitro. The obtained data indicate the absence of toxic effects up to the maximum concentrations of CeNPs (0.05 M), wherein the growth-stimulating action was shown for all samples. A dose-dependent antiviral effect of CeNPs was demonstrated. The effect was the most pronounced for VSV, which enters the cell by endocytosis and triggers fusion at low pH. The histidine-functionalized CeNPs were the most stable and had enhanced ability to reduce the viral cytopathic effect; their therapeutic index for VSV was >50 to 1000 depending on cell type. An attempt was made to explain the observed phenomena from the point of view of the physics of the synthesized particles and the biology of the virus-cell interaction.