Antiviral Mechanism of Quercetin Against Herpes Zoster by Targeting EGFR

Background: Herpes zoster, caused by the varicella-zoster virus (VZV), is an acute vesicular dermatitis with increasing incidence and severity in the elderly due to age-related immune decline. Purpose: This study aims to explore the molecular mechanism of quercetin in treating herpes zoster using a combination of network pharmacology and cell experiments. Methods: The study utilized network pharmacology to predict the targets of quercetin and VZV-related targets. A protein-protein interaction (PPI) network was constructed, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Molecular docking was used to validate the interaction between quercetin and core targets. Cell experiments were conducted to verify the antiviral effects of quercetin on VZV in HaCaT cells. Results: Network pharmacology identified 17 common targets between quercetin and VZV, with EGFR emerging as a key target. GO analysis indicated quercetin’s potential to regulate cell cycle progression, membrane-related structures, and enzyme activities. KEGG pathway analysis highlighted pathways like "EGFR tyrosine kinase inhibitor resistance". Molecular docking confirmed quercetin’s binding ability to EGFR. Cell experiments showed quercetin significantly inhibited VZV replication in HaCaT cells in a concentration-dependent manner without significant cytotoxicity. Conclusion: Quercetin exhibits promising antiviral activity against VZV through multi-target interactions, particularly by targeting EGFR. These findings suggest quercetin’s potential as a therapeutic candidate for herpes zoster treatment, warranting further in vivo and clinical studies.