Journal of affective disorders · 2025
Network pharmacology and molecular docking-based strategy to determine the potential mechanism for escitalopram-mediated long QT syndrome.
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Zhuo Chuanjun, Zhang Ying, Li Chao, Yang Lei, Zhang Qiuyu, Li Ranli, Tian Hongjun, Mao Fuqiang
Аннотация
BACKGROUND: The objective of this study was to identify the potential molecular mechanisms for escitalopram-mediated development of long QT syndrome (LQTS) using network pharmacology and molecular docking.
METHOD: Targets related to LQTS were obtained from the GeneCards, DisGeNET, and OMIM databases, while targets related to escitalopram were retrieved from the PharmMapper, SwissTargetPrediction, SuperPred, GeneCards, DrugBank, and SEA databases. A Venn diagram containing drug-disease intersection targets was generated using the Bioinformatics online tool. A protein-protein interaction network was developed using the STRING database. Core targets were screened using Cytoscape, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of escitalopram-LQTS intersection targets were performed using DAVID. A drug-disease-target pathway network was developed with Cytoscape. AutoDock Vina and PyMOL software were used for molecular docking analyses.
RESULTS: Six potential targets of escitalopram-mediated LQTS, including TNF, IL-1β, INS, SRC, STAT3, and GSK-3β, were shown to bind well to escitalopram in molecular docking analyses. The KEGG enrichment analysis suggested that escitalopram caused adverse LQTS reactions by modulating prolactin and lipid levels, atherosclerosis, and the calcium signaling pathway.
LIMITATIONS: Further in vitro or molecular biology experiments are needed to validate the mechanism identified in this study by which escitalopram induced LQTS.
CONCLUSIONS: Based on bioinformatic analysis, escitalopram may affect the electrolyte balance, atherosclerosis, and ion channels implicated in LQTS, providing theoretical clues for follow-up studies.
METHOD: Targets related to LQTS were obtained from the GeneCards, DisGeNET, and OMIM databases, while targets related to escitalopram were retrieved from the PharmMapper, SwissTargetPrediction, SuperPred, GeneCards, DrugBank, and SEA databases. A Venn diagram containing drug-disease intersection targets was generated using the Bioinformatics online tool. A protein-protein interaction network was developed using the STRING database. Core targets were screened using Cytoscape, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of escitalopram-LQTS intersection targets were performed using DAVID. A drug-disease-target pathway network was developed with Cytoscape. AutoDock Vina and PyMOL software were used for molecular docking analyses.
RESULTS: Six potential targets of escitalopram-mediated LQTS, including TNF, IL-1β, INS, SRC, STAT3, and GSK-3β, were shown to bind well to escitalopram in molecular docking analyses. The KEGG enrichment analysis suggested that escitalopram caused adverse LQTS reactions by modulating prolactin and lipid levels, atherosclerosis, and the calcium signaling pathway.
LIMITATIONS: Further in vitro or molecular biology experiments are needed to validate the mechanism identified in this study by which escitalopram induced LQTS.
CONCLUSIONS: Based on bioinformatic analysis, escitalopram may affect the electrolyte balance, atherosclerosis, and ion channels implicated in LQTS, providing theoretical clues for follow-up studies.