Dual Antiviral and Immunomodulatory Effects of Phytochemicals in Influenza A Virus Infection: Targeting Key Host Signaling Pathways.

Influenza A virus (IAV) remains a major public health threat due to its high genetic variability and ability to evade host immune responses. While antiviral drugs and vaccines remain the key measures against influenza infection, their limited efficacy and the emergence of resistant viral strains have prompted growing interest in exploring complementary therapeutic approaches. In this review, we critically evaluate current evidence on how plant-derived compounds modulate innate immune signaling networks, including toll-like receptor, retinoic acid-inducible gene I, mitogen-activated protein kinase, and nuclear factor kappa B pathways during IAV infection. We further address the pathway cross-talk that underpins this broad immunomodulatory activity, the translational barriers including bioavailability, metabolic transformation, and standardization that currently limit clinical progression, and the mechanistic gaps that future studies must resolve. Collectively, this review argues that phytocompounds should be understood as modulators of an integrated innate immune network, an insight that reframes both their therapeutic potential and the experimental standards required to advance them.