Plant-Derived Carotenoid Lutein Demonstrates Multifunctional Antiviral Activity against Influenza A Virus in vitro

Influenza virus infections remain a major global health concern, causing annual outbreaks with high morbidity and mortality. The emergence of drug resistance and adverse effects from existing antivirals underscores the need for new therapeutic agents. This study presents the first evaluation of the antiviral activity and mechanisms of the dietary carotenoid lutein against influenza viruses. Lutein exhibited strong virucidal activity against influenza A (IAV) and B (IBV) viruses, as well as Japanese encephalitis virus (JEV), but showed only weak effects against the non-enveloped rotavirus, suggesting a preference for enveloped viruses. Dynamic light scattering analysis revealed that lutein disrupted viral particle integrity, causing aggregation and a reduction in particle numbers. Functional assays further demonstrated that lutein inhibited the activities of viral hemagglutinin (HA) and neuraminidase (NA). Lutein also suppressed viral replication when applied to cells both before and after infection, indicating its prophylactic and therapeutic potential. Collectively, these findings demonstrate that lutein exerts multifunctional antiviral effects through virucidal activity, inhibition of HA and NA activity, and suppression of viral replication. As the first report to elucidate lutein's multifaceted antiviral mechanisms, this study supports its potential as a natural antiviral candidate. In vivo studies will be essential to further assess its pharmacokinetics, efficacy, and safety for therapeutic applications against influenza.