Mechanism research of Punicalagin in treating representative strains of enterovirus A and B types based on systems pharmacology and experimental validation

  • Virol J. 2025 Jul 9;22(1):229. doi: 10.1186/s12985-025-02845-0.
Yuwei Liu  #  1  2 ,  Jing Chen  #  2 ,  Nana Du  #  2 ,  Min Zhao  2 ,  Yi Zhao  2 ,  Ping Wu  2 ,  Likai Ji  2 ,  Shixing Yang  2 ,  Xiaochun Wang  2 ,  Quan Shen  2 ,  Xiaodan Zhang  3 ,  Songyi Ning  2 ,  Hongfeng Yang  4 ,  Wen Zhang  5  6
Affiliations
  • 1. Institute of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, 8 Dianli Road, Zhenjiang, 212002, China.
  • 2. Department of Bioinformatics and Intelligent Diagnosis, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212003, China.
  • 3. Department of Clinical Laboratory, Zhenjiang Center for Disease Prevention and Control, Zhenjiang, 212002, China.
  • 4. Institute of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, 8 Dianli Road, Zhenjiang, 212002, China. [email protected].
  • 5. Institute of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, 8 Dianli Road, Zhenjiang, 212002, China. [email protected].
  • 6. Department of Bioinformatics and Intelligent Diagnosis, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212003, China. [email protected].
  • # Contributed equally.
PMID: 40634970 DOI: 10.1186/s12985-025-02845-0
Abstract

Background: Enteroviruses (EVs), particularly types A (e.g., EV-A71) and B (e.g., CVB3), cause severe complications in vulnerable populations. Limited vaccines and no antivirals underscore the need for broad-spectrum therapies. Punicalagin, a natural anti-inflammatory compound, was investigated for its pan-enteroviral therapeutic potential.

Objective: To evaluate punicalagin's efficacy and mechanisms against multiple EV serotypes via integrated systems pharmacology and experimental validation.

Methods: Network pharmacology identified punicalagin's targets and pathways. In vitro Antiviral activity was assessed in Vero/A549 cells infected with EV-A71/CVB3. Neonatal mice were intraperitoneally inoculated with these viruses to test in vivo efficacy. Molecular docking, Apoptosis assays, and inflammatory factor analyses elucidated mechanisms.

Results: Punicalagin inhibited EV-A71 and CVB3 replication in vitro and improved survival in infected mice. Systems pharmacology linked its effects to anti-apoptotic and anti-inflammatory pathways. Molecular docking confirmed interactions with Apoptosis/inflammation regulators (e.g., CASP3, TNF-α). Experimental validation demonstrated reduced viral-induced Apoptosis and suppressed IL-6/TNF-α levels.

Conclusion: Punicalagin exhibits broad-spectrum anti-enteroviral activity through dual inhibition of Apoptosis and inflammation, validated across in vitro, in vivo, and computational models. This study provides a systems-level framework for repurposing natural compounds against phylogenetically diverse EVs, addressing critical therapeutic gaps for high-risk populations.

Keywords
Anti-apoptosis; Anti-inflammation; Co-treatment of different diseases; Enterovirus; Punicalagin.
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