Abstract
Potential Mechanism of Colchicine against COVID-19 and Non-Small Cell Lung Cancer based on Network Pharmacology and Bioinformatics Analysis
Department of Rehabilitation Medicine, 1Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250355, China
Correspondence Address:
Hailiang Huang, Department of Rehabilitation Medicine, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250355, China, E-mail: 60120006@sdutcm.edu.cn
Colchicine is an alkaloid with antitumor effect isolated from Colchicum autumnale plants, it has been reported in multiple studies as a potential treatment for coronavirus disease-19 and this study applied network pharmacology and bioinformatics analysis to explore the potential mechanism of colchicine against non-small cell lung cancer and coronavirus disease-19. The R software was used to determine the differentially expressed genes of non-small cell lung cancer/coronavirus disease-19, and carry out prognostic analysis and clinical analysis of the differentially expressed genes, the targets of colchicine were obtained from various databases, the protein-protein interaction network of intersection targets of colchicine and non-small cell lung cancer/coronavirus disease-19 was constructed, enrichment analysis of gene ontology and kyoto encyclopedia of genes and genomes pathways was performed by Metascape database and the molecular docking and molecular dynamics simulation were completed. We obtained a total of 716 differentially expressed genes and identified 13 potential prognostic genes associated with the clinical characterization of non-small cell lung cancer/coronavirus disease-19 patients. C-C motif chemokine ligand 2, toll like receptor 4, intercellular adhesion molecule 1, peroxisome proliferator activated receptor gamma, interleukin 17A, interferon gamma, angiotensin I converting enzyme, fos proto-oncogene, nuclear factor kappa B inhibitor alpha, TIMP metallopeptidase inhibitor 1 and secreted phosphoprotein 1 were core targets. The intersection targets of colchicine and non-small cell lung cancer/coronavirus disease-19 were mainly enriched in biological processes such as inflammatory response, response to cytokine and response to lipopolysaccharide, as well as signal pathways such as interleukin 17 signaling pathway, hypoxia inducible factor 1 signaling pathway and nucleotide binding oligomerization domain-like receptor signaling pathway. The results of molecular docking showed that the colchicine is better combined with the core targets. Analysis of molecular dynamics simulation showed that the protein and ligand form a stabilizing effect. Based on bioinformatics analysis and network pharmacology, we obtained biomarkers that may be used for the prognosis of non-small cell lung cancer/coronavirus disease-19 patients and revealed that colchicine may play a potential role in the treatment of non-small cell lung cancer/coronavirus disease-19 by regulating multiple targets and multiple signaling pathways and participating in multiple biological processes.
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