P. hybridus Extract Ze 339 Inhibits RSV Infection by Altering Host Metabolism.

Respiratory syncytial virus (RSV) remains a major cause of severe respiratory disease worldwide, particularly affecting young children and immunocompromised individuals, highlighting the need for additional therapeutic strategies. In this study, the antiviral activity of the Petasites hybridus extract Ze 339 was investigated in RSV-infected cell-culture models. Antiviral efficacy was assessed using plaque reduction assays, reporter virus analyses, and proteomic profiling to elucidate potential mechanisms of action. Ze 339 potently reduced the infectivity of both RSVA and RSVB in vitro and retained antiviral activity when administered up to six hours post-infection, resulting in markedly reduced plaque formation and viral protein biosynthesis without inducing cytotoxicity. Proteomic analyses revealed that Ze 339 modulates host cell pathways associated with reduced cell proliferation, attenuated immune signaling, and enhanced cholesterol and lipid metabolism. These changes were more pronounced in infected than in uninfected cells and coincided with a marked downregulation of viral proteins. The observed proteomic signature suggests a host-directed antiviral effect and identifies altered lipid metabolism and cell-cycle-associated pathways as potential contributors to reduced RSV replication. Taken together, these findings demonstrate the antiviral activity of Ze 339 against RSV and support the hypothesis that modulation of host cell pathways contributes to its antiviral effects, providing a rationale for further evaluation of Ze 339 as a repurposed therapeutic candidate for RSV infection.