Molecular Docking Analysis of Some Nrf2 Activators as Therapeutic Agents for the Control of Schistosomiasis

This study assessed the antischistosomal potentials of Curcumin, resveratrol and sulforaphane in silico . Sequences of Schistosoma mansoni adenylate cyclase, farnesyl diphosphate synthase, geranylgeranyl diphosphate synthase and thioredoxin glutathione reductase were retrieved from UniProt database, then used to query AlphaFold database for structural similarity and the predicted 3D structures were downloaded and saved in PDB format. Curcumin, resveratrol and sulforaphane were searched in PubChem and their 3D structures downloaded in sdf format. The enzymes and ligands were individually imported into PyRx virtual screening tool, underwent universal force field preparation before being converted to the pdbqt format. Molecular docking was then conducted and the interactions visualized using Biovia discovery studio visualizer. The absorption, distribution, metabolism, excretion and toxicity (ADMET) characteristics of the ligands were predicted in ADMETlab3.0. Resveratrol and Curcumin had the highest binding affinities of -8.0 and − 7.4 kcal/mol, respectively with S. mansoni adenylate cyclase. A similar pattern was observed between S. mansoni farnesyl diphosphate synthase with the compounds. Curcumin had the highest binding affinity (-8.5 kcal/mol) with S. mansoni geranylgeranyl diphosphate synthase, followed by resveratrol (–6.9kcal/mol). Binding affinities of -8.0, -7.5, and − 3.3 kcal/mol were exhibited by the complexes of S. mansoni thioredoxin glutathione reductase with curcumin, resveratrol and sulforaphane respectively. The compounds have all passed the Lipinski’s rule of five. Conclusively, curcumin is the most potent inhibitor of S. mansoni thioredoxin glutathione reductase and geranylgeranyl diphosphate synthase, followed by resveratrol, while resveratrol showed most promising activity against S. mansoni adenylate cyclase and farnesyl diphosphate synthase, followed by curcumin.