Formulated curcumin exerts potent anti-influenza activity by inhibition of Akt activation and viral genome replication.

Introduction: Influenza A viruses (IAVs) cause not only seasonal epidemics but also pandemics in humans. The emergence of H5N1 variants resistant to oseltamivir highlights the need to develop new antiviral therapeutic strategies. Accumulated evidence has indicated the potent anti-influenza activity of curcumin (Cur). Nevertheless, the unsatisfactory bioavailability of Cur limits its clinical use. Methods: In the present study, the anti-influenza activity and underlying mechanism of encapsulated curcumin in nanoparticle form, referred to as Cur-micelle (Cur-M), were evaluated. Results: Our results demonstrated that, as with native Cur treatment, Cur-M treatment remarkably reduced IAV infection. Interestingly, Cur-M significantly inhibited IAV infectivity post-viral entry, while treatment with Cur alone showed no effect, as demonstrated by differences in plaque formation ability. By monitoring intracellular processing, including the signaling pathway required for IAV propagation and the critical viral replication step, we discovered that viral RNA replication and the activation of Akt signaling were significantly suppressed under Cur-M treatment. Conclusion: This study depicts for the first time that Cur in its encapsulated form (i.e. Cur-M) can interfere with the intracellular machinery required for influenza infection. Cur-M could be the ideal form to evaluate the potential bioactivity of Cur in not only cell-based systems but also other in vivo systems, highlighting its potential for clinical applications.