One of the main advantages of using NPs compared to oxidized metals relies on the slow release of ions and clusters from these particles, leading to an enhancement of the antiviral activity. Additionally, the use of metal NPs containing Cu or Fe in ionic form catalyzes the generation of radicals via Fenton and Fenton-like reactions oxidizing the capsid proteins and consequently blocking the viral infection at early stage. For instance, copper ions (derived from sulfates or iodide salts) have been widely used as antiviral agents because of their activity on several kinds of enveloped and non-enveloped viruses including influenza virus,49−51 herpes simplex virus52−54 and hepatitis A virus.55 Their mechanism of action relies on the formation of Cu+ ions (from soluble salts or nanoparticles) that generate hydroxyl radicals.56 The use of metallic copper nanostructures in the form of particles or sheets has shown only a moderate efficiency due to the low concentration and low release of Cu+.56 For these reasons, Cu+ salts, where the copper ions are readily present in their active monocationic form, have been favored. In particular, CuI nanoparticles (stable at room temperature) have been extensively studied for deactivation of feline calicivirus56 and H1N1 pandemic influenza virus.57 However, the use of copper salts at high concentrations can irreversibly alter reactive oxygen species (ROS) homeostasis of healthy cells, provoking a general toxicity for the organism, limiting their applications to disinfection.56 Nanostructured cuprous and cupric oxides have been also extensively employed as antiviral agents for in vitro applications. For instance, cuprous oxide nanoparticles (CuONPs) were successfully employed against hepatitis C.58 In particular, it was found that these NPs exerted a favorable antiviral activity with no cytotoxic effects. CuONPs target the binding and entry step of viral infection to hepatic cells (Figure 5). Similar results were reported on the use of CuONPs against HSV-1, however without any profound investigation on the antiviral mechanism.59