A plant gallotannin pentagalloyl d-glucose elicits antiviral activity against influenza A and B viruses through multi-targeting mechanisms.

Influenza virus infection remains a major threat to human health. Considerable antigenic diversity and variability of influenza viruses underpin the need for the development of novel antiviral agents against the viruses. In this study, we examined the antiviral activity of pentagalloyl D-glucose (PGG), a plant gallotannin, against influenza A and B viruses. PGG showed strong virucidal activity against influenza A and B viruses at noncytotoxic concentrations. Time-of-addition experiments revealed that PGG exerted potent antiviral activity irrespective of the timing of treatment (pre-infection, during infection, or post-infection). Of note, PGG was shown to have potent inhibitory activity against both influenza A and B viral neuraminidases (NA) than oseltamivir phosphate (OP), the prodrug of the most widely used antiviral drug against the viral infections. Significantly higher binding affinity of PGG to influenza NA protein than OP was substantiated by surface plasmon surface analysis. PGG also suppressed the viral gene expression in virus-infected cells when PGG was added to cells before and after viral infection, suggesting that the antiviral activity of PGG was shown both outside and inside the cells. Comparative analyses of antiviral activity between PGG and OP demonstrated that PGG has multi-target antiviral mechanisms involving virucidal activity, HA inhibition, NA inhibition, and replication inhibition in cells. Our data demonstrate the promising potential of PGG to be an attractive antiviral agent against influenza A and B virus infections.