A Comprehensive Review - Approaches to Advance Drug Discovery for Neglected Tropical Diseases

Abstract

Background: Neglected tropical diseases (NTDs) represent a group of more than 20 infectious conditions that disproportionately affect impoverished populations in tropical and subtropical regions worldwide. Despite collectively afflicting over 1.7 billion people globally, NTDs remain severely underfunded and underrepresented in mainstream pharmaceutical research pipelines.

Objective: This review critically examines the multifaceted scientific, technological, and structural approaches that have emerged to accelerate drug discovery and development for NTDs, addressing both scientific and access-related barriers.

Methods: A comprehensive literature review was conducted using PubMed, Scopus, Web of Science, and Clinical trials.gov, covering publications from 2000 to 2024. Search terms included "neglected tropical diseases," "drug discovery," "phenotypic screening," "computational drug design," "drug repurposing," and related terms.

Results and Discussion: Eight major strategic approaches are identified and discussed: (1) target-based drug discovery exploiting validated molecular targets; (2) phenotypic and whole-organism screening; (3) drug repurposing and repositioning; (4) natural product-based drug discovery; (5) computational approaches including artificial intelligence and machine learning; (6) open-access drug discovery and collaborative models; (7) advanced drug delivery systems; and (8) public–private partnerships and product development partnerships (PDPs). Importantly, lessons from biologic drug discovery in autoimmune diseases including precision immunotherapy platforms validated for pemphigus vulgaris, generalized myasthenia gravis, and psoriasis offer translatable frameworks applicable to NTD drug development.

Conclusion: Advancing drug discovery for NTDs requires a paradigm shift integrating innovative science with sustainable funding models, open data sharing, and equitable access policies. The convergence of computational biology, open-source drug discovery, and product development partnerships represents the most viable pathway toward safe, effective, and affordable medicines for the world's most vulnerable populations.