Multi-Target Mechanistic Evaluation of Tailaparna (Eucalyptus globulus Labill.) Against Chronic Obstru ctive Pulmonary Disease and COVID-19: A Network Pharmacology and Molecular Docking Study

Abstract

Introduction: COVID-19 and chronic obstructive pulmonary disease (COPD) are two most important respiratory diseases associated with oxidative stress, inflammation, and metabolic dysregulation. The limitations and adverse effects of current treatment methods need the advance and safer multi-target therapeutic drugs. Tailaparna (Eucalyptus globulus) possesses several bioactive phytochemicals with anti-inflammatory, antioxidant, and
immunomodulatory properties that may support with respiratory disorders. Aims: The aim of the study was to explore the therapeutic potential and molecular mechanisms of E. globulus against COPD and COVID-19 using Network Pharmacology and Molecular Docking methods. Materials and Methods: E. globulus phytochemicals were screened from Dr. Duke’s and IMPPAT databases, and SwissADME was used to screen them according to Lipinski’s rule, oral bioavailability, and GI absorption. BindingDB and UniProt databases were used to find potential targets. The GeneCards and Human Protein Atlas databases provided disease-related targets for COVID-19 and COPD. Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis and the STRING database were used to analyse common targets. Phytochemical-target-pathway networks were built using Cytoscape 3.7.2. PyRx and BIOVIA Discovery Studio were used for molecular docking. Results: A total of 294 active phytochemicals and 91 related targets were identified. Between them, 55 overlapping targets for COPD and 57 for COVID-19 were detected. KEGG analysis revealed metabolic pathways, PI3K-Akt signaling pathway, Mitogen-activated protein kinase signaling pathway, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, and proteoglycans in cancer as important pathways involved in both diseases. Molecular docking proved that Ellagic acid showed the highest binding affinity with PRKACA in COPD (−10.8 kcal/mol) and IGF1R in COVID-19 (−8.4 kcal/mol). Quercetin and Luteolin also showed strong interactions with EGFR. Conclusion: E. globulus demonstrated promising multi-target therapeutic potential against COVID-19 and COPD by modifying metabolic, oxidative stress, and inflammatory pathways. Further experimental and clinical research is required to validate these findings.