A Pathogen-Hopping Approach for the Identification of Compounds with Multistage Antischistosomal Activity

"Pathogen-hopping" is an approach in infectious disease research with potential to expedite drug discovery. This is done by testing agents which are active against one or more pathogens in a new pathogen, exploiting the fact that orthologues of protein targets essential for survival exist across different pathogens. In some cases, these compounds possess selectivity versus the human orthologue, further aiding the process. To identify new lead compounds for our schistosomiasis drug discovery program, we adopted this approach by first mining the literature to find antimalarial compounds which had not been evaluated against Schistosoma. Next, a filtering process was applied to remove undesirable or potentially toxic compounds. The triaged set of compounds was then screened against Schistosoma mansoni schistosomula and adult worms. Two chemotypes displayed schistosomula and adult worm paralysis activity. Hit assessment was completed for one of these multistage actives to assess its potential for development as an antischistosomal treatment.