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Current Drug Discovery Technologies

Editor-in-Chief

ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

Research Article

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

Author(s): Priscilla Masamba, Geraldene Munsamy and Abidemi Paul Kappo*

Volume 18, Issue 5, 2021

Published on: 01 October, 2020

Article ID: e01102020186453 Pages: 14

DOI: 10.2174/1570163817666201001122436

open access plus

Abstract

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.

Keywords: Docking, G4LZI3, MD simulations, polyphenols, praziquantel, schistosomiasis.

Graphical Abstract

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