The last decades have been characterized by increasing investigation on viruses. In particular, their surface charge, protein composition, and host cell entry mechanism have been elucidated, allowing to formulate the first-generation wide spectrum antivirals. Blocking the viral entry is one of the most common known antimicrobial procedure to stop infections at the early stage. In this context, antiviral materials have been used for surface disinfection or for epidemic limitation in humans and animals. Due to their high surface to volume ratio, composition, and tunable surface chemistry, HNMs are now more and more studied as powerful agents in blocking viral entry. As for other biological interactions, the attachment and entry of viruses into host cells are mediated by multivalent interactions between the surface of the virus and cell surface receptors.10 Nanomaterials can display multivalency that makes them able to compete with the host cells on virus attachment, limiting their infectivity. The mechanism of antiviral actions relies on the inactivation of the capsid proteins. As a matter of fact, HNMs have been used for: (1) blocking target proteins for viral entry, (2) capsid protein oxidation, (3) mimicking cell surface, and (4) mechanical rupture of viruses (Figure 1). These strategies target proteins and mechanisms of entry common in most of the viruses, thus allowing the preparation of wide spectrum antiviral agents. In this section, the application of different HNMs as powerful inhibitors of viral entry will be discussed.