Exploration of American Elderberry Bioactive Compounds for Inhibition of the Influenza Virus Polymerase Acidic Endonuclease

Dwikarina, A.; Hsieh, H.; Greenlief, M.; Thomas, A. L.; Lin, C.-H.

doi:10.1101/2025.11.12.688002

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bioRxiv · 10.1101/2025.11.12.688002

Exploration of American Elderberry Bioactive Compounds for Inhibition of the Influenza Virus Polymerase Acidic Endonuclease

Dwikarina, A.·Hsieh, H.·Greenlief, M.·Thomas, A. L.·Lin, C.-H.

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Abstract

Elderberries have been commonly used to relieve symptoms of influenza and the common cold. In this study, the antiviral activity of juices of American elderberry (Sambucus nigra subsp. canadensis) cultivars were evaluated against the recombinant N-terminal domain of Influenza A Polymerase Acidic protein using a Fluorescence Resonance Energy Transfer (FRET)-based endonuclease assay. The American elderberry cultivar Ozark showed the strongest inhibitory activity among 21 cultivars, followed by the wild accession 1196. The juice from four American elderberry cultivars Ozark, accession 1892, 1196, and 2084 demonstrated stronger inhibitory effect against nPA protein (>65% inhibition) compared to the European elderberry cultivar Haschberg, which showed 62% inhibition, suggesting a higher abundance of bioactive compounds in these cultivars, capable of interfering with Influenza PA activity. Among the elderberry compounds tested, gallic acid (IC50 11.56 {+/-} 1.80 {micro}M), myricetin (IC50 16.02 {+/-} 0.06 {micro}M), caffeic acid (IC50 22.75 {+/-} 0.9 {micro}M), and luteolin (IC50 27.92 {+/-} 0.72 {micro}M), showed the strongest inhibition of nPA endonuclease activity. These findings support the application of American elderberry in nutraceutical product formulations designed to help manage flu symptoms. To the best of our knowledge, this is the first study elucidating the anti-influenza mode of action of American elderberry against influenza molecular targets.

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Dwikarina, A., Hsieh, H., Greenlief, M., Thomas, A. L., Lin, C.-H.. 2025-11-12. Exploration of American Elderberry Bioactive Compounds for Inhibition of the Influenza Virus Polymerase Acidic Endonuclease. https://doi.org/10.1101/2025.11.12.688002

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