Identifying Novel Drug Targets in Schistosoma mansoni Using Comparative Proteomics of Nigerian Field Isolates

The limited drug arsenal for schistosomiasis, based almost exclusively on praziquantel, creates a critical vulnerability in global control efforts, and identification of novel drug targets using proteomics of authentic African field isolates is a research priority. This doctoral study employed comparative proteomics to identify novel drug target candidates in S. mansoni field isolates from Plateau State, North Central Nigeria. Adult worm pairs recovered from experimentally infected mice challenged with field-derived miracidia were subjected to two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and mass spectrometry-based proteomics. Proteomes of praziquantel-sensitive versus -tolerant worm populations were compared. In silico target prioritisation was performed using druggability assessment, essentiality prediction from RNAi functional genomics databases, and human ortholog selectivity analysis. A total of 324 differentially expressed proteins were identified between sensitive and tolerant populations. Twelve proteins met target prioritisation criteria, including thioredoxin glutathione reductase (TGR), phosphoglycerate kinase, and a novel heat shock protein variant with no identified human ortholog. Molecular docking simulations identified two FDA-approved compounds with predicted binding affinity to the novel heat shock protein variant. These findings expand the druggable proteome landscape for S. mansoni and provide prioritised targets for experimental validation in the Nigerian parasite genetic background. Keywords: Schistosoma mansoni, comparative proteomics, drug targets, thioredoxin glutathione reductase, Plateau State.