Exploring therapeutic potential of repurposed drugs in chagas disease: An integrated network pharmacology and molecular docking approach

Abstract

Chagas disease, a neglected tropical illness caused by Trypanosoma cruzi characterized by severe inflammatory response and lethal cardiac complications, making traditional chemo-therapeutics inefficient. Through advanced molecular docking techniques and Network pharmacological approach, we screened 20 FDA approved orphan drugs against Chagas disease to identify their possible mechanism of action. Further these targets were validated by reviewing series of case studies conducted in patients with Chagas disease. Initially the 20 FDA approved drugs were subjected to molecular docking against Trypanosoma cruzi glucokinase. Thirteen Promising drugs with strong binding affinity were chosen for pharmacogenomic profiling through network pharmacology analysis to elucidate complex drug-target-disease relationships, potential therapeutic mechanisms and drug re-purposing opportunities. Our integrated methodology revealed that drugs like Belumosudil, Quizartinib, Vomorolone, Voydeya and Zanubritinib are directly involved in pathways related to Chagas disease. Further docking analysis was conducted between these drugs and their respective highly interacting gene. A detailed case report analysis confirmed their role in pathogenesis of T. cruzi infection. Other 8 drugs are found to be indirectly effective by targeting inflammatory pathways of disease progression. This research presents a multifaceted investigation integrating molecular docking, network pharmacology, and clinical case analysis to explore novel therapeutic strategies for managing the disease.