Closing the Gap: An Atomistic Structural and Functional Perspective of S. mansoni Universal Stress G4LZI3 Protein in Complex with Phenolic Compounds

Priscilla Masamba, Geraldene Munsamy, Abidemi Paul Kappo

Research output: Contribution to journalArticlepeer-review


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 highlight-ing 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 inte-gration 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.

Original languageEnglish
Article numbere01102020186453
JournalCurrent Drug Discovery Technologies
Issue number5
Publication statusPublished - Sept 2021


  • Docking
  • G4LZI3
  • MD simulations
  • Polyphenols
  • Praziquantel
  • Schistosomiasis

ASJC Scopus subject areas

  • Drug Discovery


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