Recent Developments to Fight Multidrug Resistance (MDR) in Protozoa

This chapter focuses on the solutions to emerging multidrug resistance in the major parasitic protozoa plaguing the world. These neglected pathogens have seized the developing nations in a vice-like grip and are seeping into the industrialised world with the dramatic increase in global travel. The alarming rise in resistance to most antiparasitic drugs has left even the wealthiest nations vulnerable. Multidrug resistance occurs to give a survival advantage to the parasite; it has been hastened by the uncontrolled use of chemotherapeutics. This chapter categorises the recent developments to overcome the MDR hurdle under different approaches. The synthesis of novel organic compounds and high-throughput screenings of new chemical entities are two major approaches. Protease and topoisomerase inhibitors of parasitic protozoa prove as worthy drug targets. In-silico and proteomics-based methods also accelerate drug discovery by creating potential drug libraries specific to tropical protozoa. A costeffective and rapid method of combating drug resistance is the repurposing of licensed medicines. This approach also accounts for the established safety of drugs and high commercial availability. Molecular advancements have introduced small interfering RNAs (siRNAs) at preclinical levels as therapeutics functioning via a unique mechanism. The nanoparticle and cell-penetrating peptides (CPP) based delivery of siRNAs has facilitated a stable and low toxic way to silence genes providing pathogenicity and resistance. This will help in reversing MDR and breathing new life into the existing licensed antiprotozoal chemotherapies. 

Keywords: Antimicrobial peptides, Antiprotozoal therapeutics, Aystems biology, Drug repurposing, In-silico, Multidrug resistance, Protease inhibitors, siRNA, Synthetic organic compounds.