Discovery of Natural Multi‐Target Neuraminidase Inhibitors Anti‐Influenza Virus from Chinese Medicinal Herbs Containing Coumarin: In Silico and In Vitro Experiments

During in silico research, based on molecular docking, dynamics simulation, network pharmacology and ADMET (absorption, distribution, metabolism, excretion, and toxicity) property, 31 potential compounds are obtained from seven Chinese medicinal herbs containing coumarins. Moreover, mechanism researches discover these compounds treat influenza A virus through key targets TLR4, MMP9, and IL6 (high fever, acute respiratory distress syndrome), MAPK1 and MAPK3 (MAPK signaling pathway, viral RNP export and viral protein expression), CASP3 (apoptosis), EP300 and CREBBP (viral myocarditis, chemoattraction of monocytes and macrophages, T cell activation antibody response). Further experimental verification finds that 22 of 31 compounds have various degrees of anti‐influenza virus activities. Moreover, 12 of 22 compounds have better biological activities (IC50=0.1609–54.95 μM) than oseltamivir (IC50=114.3 μM). 3 of 12 compounds have better antioxidant activities (IC50=2.087–3.796 μM) than vitamin C (IC50=5.004 μM). Therefore, ellagic acid, hyperoside, and fraxetin are promising multi‐target lead compounds for influenza virus therapy. Meanwhile, the present study offers compelling evidence for the development of novel antiviral medications. In order to obtain new natural multitarget neuraminidase inhibitors (NIs) drugs, this research comprehensively utilized molecular docking, molecular dynamics simulation, network pharmacology, and in vitro experimental verification. Mechanism researches discover these compounds treat influenza disease through EGFR, IL6, and MMP9 targets. Further experimental verification finds that Ellagic acid, Hyperoside, and Fraxetin are discovered as optimal NIs lead compounds.