In addition, interfering with this very first step in viral pathogenesis could have strong prophylactic effects as well. Understanding this significance of HS in the infection process, along with recent advances in nanotechnology, spurred on the development of metal oxide based nanostructured compounds that mimic the viral binding ability of HS. One of these nanostructures, zinc oxide, studied in our lab, has already shown this ability to compete for viral binding and suppress HSV-1 infection by such an emulating mechanism. The cause of this attraction resides in the similar charge and shape comparable to the natural target. Nanostructures from other metal based materials have also shown similar antiviral properties such as silver nanoparticles capped with mercaptoethane sulfonate and gold nanoparticles capped with mercaptoethane sulfonate. This mechanism is also shared with sulfated polysaccharides, and sulfated nonpolysaccharides, ). One of the latest nanostructures yet to be tested is tin oxide nanowires, the subject of this paper. In this study we investigated the potential of the negatively charged surface of SnO2 nanowires to bind and trap HSV-1 before entry into host cells. Here, through multiple biochemical and molecular based assays, we demonstrate the ability of SnO2 to significantly inhibit HSV-1 entry, replication, and cell-to-cell spread in naturally susceptible human corneal epithelial cells. So far herpes simplex virus type 1 has eluded a cure. Although there are many anti HSV-1 drugs available to treat symptoms, they do not eliminate the virus or stop the spread of existing virions, and severe complications such as blindness and encephalitis are still possible. This is especially true in neonates and immunocompromised patients. Drug resistance has also been reported in the latter. One way the effects of current therapies against HSV can be enhanced is by targeting multiple steps in HSV pathogenesis. Multi-targeted therapy against HSV has not been possible due to lack of well-studied new targets. Therefore, the development of alternate antiviral agents needs to be a top priority for this highly contagious global disease. Targeting entry and more specifically HS attachment during viral pathogenesis with SnO2 appears to fulfill this requirement and shows the promise of providing great benefits in multi-drug therapy against HSV. Since attachment to cell surface HS is the first step in the infection process for many viruses, including HSV-1, it should naturally be an attractive model for an antiviral defense mechanism. And of course, blocking entry has the added advantage of minimizing or eliminating all of the following steps in the infectious cycle. In these experiments SnO2 nanowires have shown an ability to compete for virus at the attachment step by acting like the natural target, similar to what ZnO, Ag-MES, and Au-MES do. Since the amount of virus that enters the cell has a direct relationship with disease severity and reactivation rates, minimizing or blocking the viral load with SnO2 is certainly expected to substantially reduce the distressful and sometimes agonizing results of an untreated infection. In keeping with its emerging biological applications and relatively non-toxic nature under in vitro conditions, the SnO2 nanowires used here were found to be an effective inhibitor of viral entry and cell-to-cell spread. The concentrations of SnO2 used in our study were well below any significant cytotoxic levels. The results on average showed a 75% reduction in cell entry, 77% smaller plaques or infected cell clusters and over a 99% drop in cell-to-cell fusion. Reduced entry also translated into reduced Dabrafenib replication and spread to other cells.