Besides the composition of the metal core, several studies have pointed out the importance of the control of the surface chemistry. The surface groups can: (1) stabilize NPs in the biological media, (2) insert targeting agents, and (3) enhance the circulation time inside the body. Antiviral efficiency can be also enhanced by the multivalency effect, where highly branched ligands are used to locally augment the local concentration of the targeting molecules. In this section the main strategies and results for silver (AgNPs) and gold (AuNPs) nanoparticles in blocking viral entry will be critically discussed.