Interactions Of Anti-Viral Ceria Nanoparticles With An Enveloped RNA Virus

There is growing interest in developing durable and broad-spectrum antiviral nanomaterials for surface disinfection. Silver-modified ceria nanoparticles (AgCNPs) are regenerative materials capable of inactivating a wide range of viruses through generation of reactive oxygen species (ROS). We hypothesized that for enveloped RNA viruses, the lipid bilayer and viral spike glycoproteins are determinants of sensitivity to inactivation of infectivity by AgCNPs. This hypothesis was tested using Vesicular Stomatitis Virus (VSV), a model enveloped negative-sense single strand RNA virus containing a single spike glycoprotein G. Five rounds of serial passage of VSV in the presence of suboptimal AgCNP concentrations led to the emergence of a virus population which had gained resistance to inactivation by AgCNP. Growth time courses and realtime assays for cell killing showed that the resistant VSV population had gained the properties of accelerated growth kinetics and enhanced cytopathic effects compared to the parental AgCNPsensitive virus. VSV derived from a range of cell lines was generated to test the role of varying viral lipid envelope in AgCNP sensitivity –the various cell line-derived VSV did not substantially differ in sensitivity to AgCNPs. However, the presence of biological interfering media, such as fetal bovine serum (FBS) and red blood cells (RBCs), transiently reduced nanoparticle efficacy depending on reaction time and concentration of soil load. Taken together, our findings demonstrate that an enveloped RNA virus can evolve resistance to AgCNPs under sustained selective pressure and that this acquired AgCNP resistance is associated with other accelerated properties of the virus. These results provide important insights into nanoparticle–virus interactions in real world scenarios and the potential for resistance emergence, informing the future development of nanomaterial-based antiviral strategies.