Innate immune response is the first response that takes place in the presence of any type of infection. During this early stage, interferon stimulating genes (ISGs) are upregulated in the infected cells.125 This self-defense mechanism slows down the viral replication and alerts sentinel immune cells that start producing proinflammatory cytokines and trigger inflammation.125 However, many viruses are able to escape this complex mechanism, retarding the immune response and spreading the infection. The interaction of HNMs with the immune system has been more and more studied. In the case of antiviral HNMs, many examples can be found in the literature where the NMs not only slow down the infection but also tune the innate immune response. Certain HMNs can display an intrinsic immune stimulation. We have already mentioned above that in the early stage of infection, AgNPs mainly prevent the virus from entering the host cell through the interaction with the external capsid, but in vitro cellular experiments lack to understand the complex interaction with primary immune cells. Recent studies have shown that AgNPs can potentially induce the expression of genes involved in innate and adaptive immunity-associated pathways, which are known to play crucial role in immune regulation. For example, Toll-like receptor 7 can be upregulated by AgNPs after 24 h, by recognizing the single-stranded RNA of the viruses and regulating the antiviral immune response.126 Another study showed that in RSV-infected mice treated with AgNPs, the particles reduced the production of pro-inflammatory TNF-α and IL-6 cytokines, but potentiated the anti-RSV activity of neutrophils in an experimental mouse model.127 However, activation of AgNPs in the reduction of RSV has been noted only when the NM was intranasally inoculated together with the virus, and no results have been reported on the use of AgNPs administrated on infected mice. In the case of influenza virus infection of lung epithelial cells, it was found that AgNPs targeted infected lung epithelial cells and reduced viral replication, by preventing autophagy. However, the blockage of the autophagic flux by AgNPs does not inhibit viral replication in already infected cells. Therefore, AgNPs are more suitable as viral preventive agents due to their pro-inflammatory response rather than drugs.128 More recently, AgNPs were combined with graphene materials and exploited as antiviral material for the treatment of Porcine reproductive and respiratory syndrome virus (PRRSV).129 GO-AgNPs were able to clump the virus diminishing its fusion with cell membrane. Additionally, once GO-AgNPs were internalized in host cells, they stimulated the ISGs that blocked viral budding and its diffusion to other cells in vitro (Figure 15).129