According to our results, this mode of antiviral action allows silver nanoparticles to inhibit HIV-1 infection regardless of viral tropism or resistance profile, to bind to gp120 in a manner that prevents CD4-dependent virion binding, fusion, and infectivity, and to block HIV-1 cell-free and cell-associated infection, acting as a virucidal agent. Here, CD4 is linked to HIV-1 infection.