Harnessing Drug Repurposing and Polypharmacology for Therapeutic Innovation in Neglected Tropical Diseases (NTDS)

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Abstract
Neglected tropical diseases (NTDs) continue to place a heavy burden on low- and middle-income countries. In these regions, drug development is often slow and expensive, and NTDs are rarely a priority due to limited financial incentives and complex science. This chapter looks at how combining drug repurposing and polypharmacology can offer faster and more affordable ways to discover treatments for NTDs. Using ideas from computational systems biology, we outline both a theoretical and practical approach to exploring lesser-known drug targets through multi-target strategies. We highlight modern computer-based tools, like network pharmacology, omics data analysis, and machine learning, that help identify new links between drugs and diseases in both humans and pathogens. We focus especially on in silico (computer-based) drug repurposing pipelines and how databases like DrugBank, ChEMBL, and SchistoDB can help match existing drugs to neglected diseases. Real-life examples, such as Miltefosine for leishmaniasis, the broad potential of Ivermectin, and using statins to treat schistosomiasis, show how targeting multiple disease pathways can be effective. The chapter also addresses challenges, such as gaps in our understanding of pathogens, drug delivery issues, and regulatory barriers, especially in settings with fewer resources. Looking ahead, we support moving toward more precise tropical medicine by combining genetic and biological data with AI tools, while keeping research ethically and inclusive of local communities. In summary, the chapter shows how drug repurposing can be a powerful and fair way to improve treatment options for neglected diseases.