Maoto Is Associated With Partial Recovery of Autophagic Flux in Influenza Virus‐Infected A549 Cells

ABSTRACT Aim Influenza A virus subverts host autophagy by impairing autophagosome–lysosome fusion, a strategy that supports viral replication. Maoto, a traditional Kampo medicine, exhibits antiviral activity against influenza through multiple mechanisms. This study aimed to examine whether maoto is associated with modulation of autophagy during influenza virus infection. Methods A549 cells were infected with influenza A/PR8 virus at a multiplicity of infection of 1. Viral titers were quantified by TCID 50 assays using MDCK cells. Autophagy‐related processes were analyzed using GFP‐LC3, Lysotracker staining, and LC3 turnover assays. siRNA‐mediated knockdown of Beclin 1 and Atg14 was performed to assess the contribution of autophagy to the antiviral effects of maoto. Results Maoto significantly reduced viral titers when administered before or during the early phase after viral entry. Influenza virus infection induced perturbations of autophagic flux, characterized by accumulation of immature autophagosomes. Maoto treatment partially counteracted these alterations in autophagic flux. Knockdown of Beclin 1 or Atg14 attenuated, but did not abolish, the antiviral activity of maoto. Conclusion These findings suggest that modulation of autophagy contributes to the antiviral activity of maoto during influenza virus infection. Partial alleviation of virus‐induced autophagy impairment may represent one of the complementary host‐directed mechanisms underlying the multifaceted antiviral effects of this traditional medicine.