Insights into the direct anti-influenza virus mode of action of Rhodiola rosea

•Beside flavonoids, tannins mainly including prodelphinidin gallate oligomers, mediate the strong anti-influenza virus activity of SHR-5.•Neither resistance to oseltamivir nor to M2 ion channel blockers hampered the strong activity of SHR-5 and its tannin-enriched fraction (TE) against influenza viruses of subtypes A and B.•The mode of action is based on the interaction of SHR-5 and TE with the viral envelope including also the inhibition of viral neuraminidase.•No development of SHR-5 resistance in influenza viruses was observed in vitro, which makes this multicomponent mixture an even more promising therapeutic candidate.