Mechanistic insights into flavonoid-mediated regulation of human influenza virus replication.

Influenza A virus (IAV) remains a major global health concern due to its rapid mutation rate, antigenic variability, and the emergence of resistance to frontline antivirals such as oseltamivir and zanamivir. Despite available vaccines and therapeutics, their limited efficacy against emerging strains underscores the urgent need for new antiviral approaches. Therefore, plant-derived bioactive compounds, particularly flavonoids, have gained attention for their ability to target both viral and host pathways, yet their mechanisms of action remain incompletely understood. This review synthesises current evidence on the antiviral potential of plant-derived flavonoid against human IAV subtypes H1N1 and H3N2. Flavonoids disrupt key stages of the viral life cycle, including attachment, entry and release, and interact with IAV proteins such as hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), and matrix-2 (M2) ion channels. The ability of plant-derived compounds to inhibit viral replication underscores their potential as leads for next-generation influenza therapeutics. Nonetheless, rigorous in vivo studies, mechanistic elucidation, and pharmacokinetic evaluations are essential to advance these candidates toward clinical translation.