Verteporfin is an effective inhibitor of HCMV replication

• HCMV poses significant risks to newborns and immunocompromised individuals. • Verteporfin is an FDA-approved medication used in photodynamic therapy. • Verteporfin inhibits HCMV progeny virus production. • Verteporfin suppresses HCMV gene expression from the immediate-early stages. • Verteporfin has the potential to be repurposed as a drug against HCMV infection. Human cytomegalovirus (HCMV), a double-stranded DNA virus from the Betaherpesvirinae subfamily, constitutes significant risks to newborns and immunocompromised individuals, potentially leading to severe neurodevelopmental disorders. The purpose of this study was to identify FDA-approved drugs that can inhibit HCMV replication through a drug repositioning approach. Using an HCMV progeny assay, verteporfin, a medication used as a photosensitizer in photodynamic therapy, was found to inhibit HCMV production in a dose-dependent manner, significantly reducing replication at concentrations as low as 0.5 µM, approximately 1/20th of the concentration used in anti-cancer research. Further analysis revealed that verteporfin did not interfere with HCMV host cell entry or nuclear transport but reduced viral mRNA and protein levels throughout the HCMV life cycle from the immediate-early stages. These results suggest that verteporfin has the potential to be rapidly and safely developed as a repurposed drug to inhibit HCMV infection.