Background: For decades, Praziquantel has been the undisputed drug of choice for all
schistosome infections, but rising concerns due to the unelucidated mechanism of action of the
drug and unavoidable reports of emerging drug resistant strains has necessitated the need for alternative
treatment drug. Moreover, current apprehension has been reinforced by total dependence on
the drug for treatment hence, the search for novel and effective anti-schistosomal drugs.
Methods: This study made use of bioinformatic tools to determine the structural binding of the Universal
G4LZI3 Stress Protein (USP) in complex with ten polyphenol compounds, thereby highlighting
the effectiveness of these recently identified ‘lead’ molecules in the design of novel therapeutics
targeted against schistosomiasis. Upregulation of the G4LZI3 USP throughout the schistosome
multifaceted developmental cycle sparks interest in its potential role as a druggable target. The integration
of in silico tools provides an atomistic perspective into the binding of potential inhibitors to
target proteins. This study therefore, implemented the use of Molecular Dynamic (MD) simulations
to provide functional and structural insight into key conformational changes upon binding of G4-
ZLI3 to these key phenolic compounds.
Results: Post-MD analyses revealed unique structural and conformational changes in the G4LZI3
protein in complex with curcumin and catechin respectively. These systems exhibited the highest
binding energies, while the major interacting residues conserved in all the complexes provides a
route map for structure-based drug design of novel compounds with enhanced inhibitory potency
against the G4LZI3 protein.
Conclusion: This study suggests an alternative approach for the development of anti-schistosomal
drugs using natural compounds.