Verteporfin is a broad-spectrum inhibitor of arboviruses and influences viral and host-based events.

There is an unmet need for broadly effective therapeutic strategies to address the globally expanding health burden caused by vector-transmitted viruses. Protein-protein interactions involving host and viral proteins are key regulators of a productive viral infection and interruption of such interactions can exert broad-spectrum antiviral outcomes. Verteporfin (VP), a small molecule that is currently approved by the United States Food and Drug Administration (FDA) for the treatment of age-related macular degeneration and a known Yes-associated protein (YAP) inhibitor, was identified as a robust inhibitor of Venezuelan Equine Encephalitis Virus (VEEV) TC-83 strain from a protein-protein interaction inhibitor library. VP demonstrated a cell type independent reduction of viral load with inhibitory mechanism including reduction of nonstructural and structural protein levels. VP treatment also impacted its known target YAP, resulting in reduced expression of total and phosphorylated YAP in virus-infected cells. The in vivo assessment of VP in a lethal infection rodent model demonstrated early promise by increasing survival of infected animals, while also indicating the need for additional improvements in dosing strategy. Assessment of VP-mediated inhibition of other RNA viruses including Old- and New-world alphaviruses, a prototype flavivirus and bunyavirus demonstrated the potential of VP to function as a broad-spectrum inhibitor of vector-transmitted viruses.