Recent Advances in Anti-Schistosomiasis Drug Discovery

Abstract

Schistosomiasis, a parasitic disease caused by infection by helminths of the Schistosoma genus, affects over 200 million people, primarily in the developing world. Treatment of this disease largely relies on one drug, praziquantel. Although this drug is cheap, safe, and effective, the looming prospect of drug resistance makes the development of a pipeline of anti-schistosomiasis drugs a priority. Many new drug leads have arisen from screening existing sets of compounds such as the Open Access Boxes developed by the Medicines for Malaria Venture (MMV) in collaboration with the Drugs for Neglected Diseases Initiative (DNDI). Other leads have been found through work focused on druggable targets such as kinases, histone deacetylases, proteases, and others. This chapter will discuss recent work concerning the discovery and development of novel anti-schistosomiasis drug leads from many sources.

Development of subunit selective proteasome substrates forSchistosoma species

“…Among the potential molecular drug targets discussed over the years for chemotherapy of schistosomiasis 6, 20 , a recent addition has been the proteasome 21, 22 which is an evolutionarily conserved, multi-subunit, ATP-dependent proteolytic complex that is vital to cellular proteostasis 23, 24 . Each 20S proteasome core comprises two stacked rings of seven β subunits between two rings of seven α subunits ( Fig.…”