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.
Uses: 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.
Conclusion:
This study therefore, implemented the use of molecular dynamic (MD) simulations to provide functional and
structural insight into key conformational changes upon binding of G4ZLI3 to these key phenolic compounds. 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. This study suggests an alternative approach for the development of anti-schistosomal
drugs using natural compounds.
The distribution of polysaccharide hydrolase activity in gastropods and bivalves.
