Exploring Therapeutic Paradigm Focusing on Genes, Proteins, and Pathways to Combat Leprosy and Tuberculosis: A Network Medicine and Drug Repurposing Approach DOI Creative Commons
Mohd Imran, Ahmed Subeh Alshrari,

Md Golam Hafiz

и другие.

Journal of Infection and Public Health, Год журнала: 2025, Номер unknown, С. 102763 - 102763

Опубликована: Март 1, 2025

Leprosy and tuberculosis caused by Mycobacterium leprae tuberculosis, respectively, are chronic infections with significant public health implications. While leprosy affects the skin peripheral nerves primarily targets lungs, both diseases involve systemic immune responses. This study integrates transcriptomic analysis cheminformatics molecular dynamics simulations to identify mechanisms potential therapeutic targets. Transcriptomic datasets were analyzed dysregulated genes pathways. Pathway enrichment tissue-specific bulk RNA-seq expression analyses provided biological context. System biology networks revealed regulatory hub docking studies evaluated CHEMBL compounds as therapeutics. Molecular (MD) assessed stability of top ligand-protein complexes through RMSD RMSF MM-GBSA free energy calculations. Gene identified 13 core genes, including HSP90AA1 MAPK8IP3 ZMPSTE24. Tissue-specific localized pivotal lung tissues cells highly expressed in alveolar macrophages epithelial cells. gene emerged a central 96 interactions involved stress response Docking CHEMBL3653862 CHEMBL3653884 strong binding affinities (-10.16 -12.69 kcal/mol) interacting Asp93 Tyr139. MD confirmed fluctuations within 2.1-3.5 Å values supporting stability. identifies drug target tuberculosis. Findings support host-directed therapy approaches highlight importance computational modeling accelerating discovery. The provides foundation for future experimental validation, vitro vivo testing advance repurposing strategies these infections.

Язык: Английский

Exploring Therapeutic Paradigm Focusing on Genes, Proteins, and Pathways to Combat Leprosy and Tuberculosis: A Network Medicine and Drug Repurposing Approach DOI Creative Commons
Mohd Imran, Ahmed Subeh Alshrari,

Md Golam Hafiz

и другие.

Journal of Infection and Public Health, Год журнала: 2025, Номер unknown, С. 102763 - 102763

Опубликована: Март 1, 2025

Leprosy and tuberculosis caused by Mycobacterium leprae tuberculosis, respectively, are chronic infections with significant public health implications. While leprosy affects the skin peripheral nerves primarily targets lungs, both diseases involve systemic immune responses. This study integrates transcriptomic analysis cheminformatics molecular dynamics simulations to identify mechanisms potential therapeutic targets. Transcriptomic datasets were analyzed dysregulated genes pathways. Pathway enrichment tissue-specific bulk RNA-seq expression analyses provided biological context. System biology networks revealed regulatory hub docking studies evaluated CHEMBL compounds as therapeutics. Molecular (MD) assessed stability of top ligand-protein complexes through RMSD RMSF MM-GBSA free energy calculations. Gene identified 13 core genes, including HSP90AA1 MAPK8IP3 ZMPSTE24. Tissue-specific localized pivotal lung tissues cells highly expressed in alveolar macrophages epithelial cells. gene emerged a central 96 interactions involved stress response Docking CHEMBL3653862 CHEMBL3653884 strong binding affinities (-10.16 -12.69 kcal/mol) interacting Asp93 Tyr139. MD confirmed fluctuations within 2.1-3.5 Å values supporting stability. identifies drug target tuberculosis. Findings support host-directed therapy approaches highlight importance computational modeling accelerating discovery. The provides foundation for future experimental validation, vitro vivo testing advance repurposing strategies these infections.

Язык: Английский

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