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Updated: Jan 17, 2026
A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
Targeting FTO/m6A epigenetics: Phillyrin dual-blocks respiratory syncytial virus replication and inflammation via
Zhu Li1, Guanghui Jin2, Xuanxuan Li2
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510230, China; The First People's Hospital of Zunyi (The Third Affiliated Hospital of Zunyi Medical University), Guizhou, Zunyi, 563000, China.
Background:
Phillyrin (KD-1), the principal bioactive component of Forsythia suspensa (Thunb.) Vahl, exhibits well-documented multifaceted anti-inflammatory and broad-spectrum antiviral activities. Notably, its specific antiviral efficacy against respiratory syncytial virus (RSV) and the underlying epigenetic regulatory mechanisms remain unexplored.
Purpose:
To delineate phillyrin's dual-targeting mechanism against RSV pathogenesis, focusing on m6A methylome reprogramming and host-virus interactome modulation.
Methods:
Employing comprehensive models spanning cellular systems, multi-age respiratory organoids, and animal models, this study evaluated the anti-RSV activity of phillyrin.
Results:
Integrated multi-model analyses demonstrate that phillyrin exhibits potent anti-RSV activity and dose-dependently suppresses virus-induced inflammation. Crucially, phillyrin significantly restored RSV-mediated global N6-methyladenosine (m6A) hypomethylation and downregulated the demethylase fat mass and obesity-associated protein (FTO). Mechanistically, FTO knockdown suppressed NF-κB/STAT3 pathway activation, with phillyrin synergistically enhancing this suppression. Conversely, FTO overexpression abolished phillyrin's inhibitory effects on these pathways. Molecular studies revealed dual targeting: phillyrin formed stable complexes with RSV-N protein, while FTO directly bound RSV-N, evidenced by co-localization in cytoplasmic compartments via laser scanning confocal microscopy.
Conclusion:
These results revealed that phillyrin combats RSV infection through a dual mechanism: Direct engagement with the viral N protein to disrupt viral function, and resolution of inflammation via FTO/m6A-mediated silencing of the NF-κB/STAT3 signaling axis.
