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

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 investiga...

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Main Authors: Yuwei Liu, Jing Chen, Nana Du, Min Zhao, Yi Zhao, Ping Wu, Likai Ji, Shixing Yang, Xiaochun Wang, Quan Shen, Xiaodan Zhang, Songyi Ning, Hongfeng Yang, Wen Zhang
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Virology Journal
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Online Access:https://doi.org/10.1186/s12985-025-02845-0
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Summary: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.
ISSN:1743-422X