Computational Screening of Natural Phytochemicals against Cystic Fibrosis: Molecular Docking and Network Enrichment Analysis

A BSTRACT Context: Cystic fibrosis (CF) is a severe genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene; this condition leads to chronic respiratory infections, gastrointestinal issues, and other life-threatening complications. Aims: The aim of this study was to investigate natural compounds as potential ligands for targeting CFTR along with functional enrichment of CFTR protein. Settings and Design: Molecular docking and computational analysis were performed to screen a library of natural compounds for their therapeutic potential against CF proteins. Subjects and Methods: Twenty-five phytomolecules were selected for docking with CF-related proteins. CB DOCK, and SwissDock Vina software were used for protein-ligand docking. Network enrichment was done using the STRING database. Statistical Analysis Used: Docking scores were analyzed to determine the binding affinities of the natural compounds. Gene ontology (GO) analysis and pathways were analyzed using background score, gene count, etc. Results: The docking results revealed that the ligands 3,5’- dihydroxythalifaboramine and camptothecin exhibited high binding affinities against targeted proteins, indicating their potential therapeutic value. Functional enrichment emphasized the importance of protein processing in the endoplasmic reticulum, intracellular transport mechanisms, and tight junction maintenance in maintaining CFTR function and localization. Conclusions: This study highlights the therapeutic potential of natural compounds in the treatment of CF by targeting CFTR and related proteins. The identified ligands show promise for further investigation through in vitro and in vivo testing to confirm their efficacy and validate their potential as new CF treatments. The study also underscores the significance of the molecular pathways involved in CFTR folding, trafficking, and cellular function, which could serve as critical therapeutic targets in CF drug discovery.