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(1) Background: Re-emerging influenza threats continue to challenge medical and public health systems. Quercetin is a ubiquitous flavonoid found in food and is recognized to possess antioxidant, anti-inflammatory, antiviral, and anticancer activities. (2) Methods: To elucidate the targets and mechanisms underlying the action of quercetin as a therapeutic agent for influenza, network pharmacology and molecular docking were employed. Biological targets of quercetin and target genes associated with influenza were retrieved from public databases. Compound–disease target (C-D) networks were constructed, and targets were further analyzed using KEGG pathway analysis. Potent target genes were retrieved from the compound–disease–pathway (C-D-P) and protein–protein interaction (PPI) networks. The binding affinities between quercetin and the targets were identified using molecular docking. (3) Results: The pathway study revealed that quercetin-associated influenza targets were mainly involved in viral diseases, inflammation-associated pathways, and cancer. Four targets, MAPK1, NFKB1, RELA, and TP53, were identified to be involved in the inhibitory effects of quercetin on influenza. Using the molecular docking method, we evaluated the binding affinity of each ligand (quercetin)–target and discovered that quercetin and MAPK1 showed the strongest calculated binding energy among the four ligand–target complexes. (4) Conclusion: These findings identified potential targets of quercetin and suggest quercetin as a potential drug for influenza treatment.

Uncovering Quercetin’s Effects against Influenza A Virus Using Network Pharmacology and Molecular Docking