The Application of Fragment-based Approaches to the Discovery of Drugs for Neglected Tropical Diseases

Abstract

The term neglected tropical disease (NTD) is used to describe a diverse collection of communicable diseases prevalent in tropical and subtropical regions, which predominantly affect the poor. The World Health Organization (WHO) currently identifies a set of twenty diseases,† chiefly caused by parasites, bacteria and viruses, as priority NTDs (WHO 2018a). Although these diseases have not attained the notoriety of the “big three” infectious diseases—malaria, tuberculosis and HIV—most are highly debilitating, several cause chronic diseases, and some are lethal. They currently affect more than a billion people in 149 countries (WHO 2018a) and impart a substantial economic and social burden, thereby perpetuating the cycle of poverty and disease. Through implementation of five main strategies (preventative chemotherapy, innovative and intensified disease management, vector ecology and management, veterinary public health services and the provision of safe water, sanitation and hygiene), great strides have been made toward the goals of controlling, eliminating and eradicating NTDs set forth by the WHO in 2012 (WHO 2017). However, in order to meet targets set for 2020 and beyond, it has become evident that new control tools, including drugs, are needed. For some NTDs no safe, affordable and orally active drugs are available, and where they are, alternatives are required for combination therapies and as backups for when efficacy is lost and/or resistance emerges. Despite the high NTD burden, in the period between 2000 and 2011, just 0.6% of new therapeutics were for neglected diseases and none of these were new chemical entities (Pedrique et al. 2013), highlighting the unmet medical need.