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Background <p>Amoebiasis is a parasitic intestinal disease caused by the protozoan Entamoeba histolytica, which is transmitted through contaminated food and liquids. It is well known for invading and destroying human intestinal tissues, leading to life-threatening abscesses.</p> Objective <p>To treat amoebiasis and reduce the parasitic infection, thioredoxin reductase (TrxR), a promising target. It catalyses the NADP-dependent reduction of amoebic thioredoxins, which is essential for maintaining intracellular redox balance. Thus, the parasitic infections may be eradicated by altering the redox state of E. histolytica through TrxR inhibition.</p> Methods <p>To identify conceivable TrxR inhibitors, an integrated in silico strategy was used, which included molecular docking, molecular dynamics (MD) simulation, steered molecular dynamics (SMD), and Molecular Mechanics/Poisson Boltzmann Surface Area (MM/PBSA) calculations.</p> Results <p>Docked FDA libraries and selected five compounds: Betrixaban, Netrasudil, Novobiocin, NADPH, and Metronidazole with TrxR—show promising interaction analysis. Furthermore, SMD-based simulation showed a high pulling force for Netrasudil and NADPH (~ 550&#xa0;kJ/mol &amp; ~375&#xa0;kJ/mol). MMPBSA, RMSD, and H-bond analysis support the notion that netrasudil interacts most effectively with the FDA compounds.</p> Conclusion <p>Our multi-tiered computational approach, evaluated as a whole, finds intriguing natural scaffolds for TrxR inhibition and provides an adequate basis for lead optimization in amoebosis treatment. Overall, Prior use of these compounds may be required for in-vitro and in-vivo evaluations.</p>

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Computational Investigation of FDA-Approved Compounds for Thiol Reductase Inhibition To Overcome Amebiasis Using Docking and SMD-based Simulation Analysis

  • 期刊论文

  • 发表日期：

    2026年2月2日

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  • Kalpana Singh,
  • Akash Pratap Singh

摘要

Background

Amoebiasis is a parasitic intestinal disease caused by the protozoan Entamoeba histolytica, which is transmitted through contaminated food and liquids. It is well known for invading and destroying human intestinal tissues, leading to life-threatening abscesses.

Objective

To treat amoebiasis and reduce the parasitic infection, thioredoxin reductase (TrxR), a promising target. It catalyses the NADP-dependent reduction of amoebic thioredoxins, which is essential for maintaining intracellular redox balance. Thus, the parasitic infections may be eradicated by altering the redox state of E. histolytica through TrxR inhibition.

Methods

To identify conceivable TrxR inhibitors, an integrated in silico strategy was used, which included molecular docking, molecular dynamics (MD) simulation, steered molecular dynamics (SMD), and Molecular Mechanics/Poisson Boltzmann Surface Area (MM/PBSA) calculations.

Results

Docked FDA libraries and selected five compounds: Betrixaban, Netrasudil, Novobiocin, NADPH, and Metronidazole with TrxR—show promising interaction analysis. Furthermore, SMD-based simulation showed a high pulling force for Netrasudil and NADPH (~ 550 kJ/mol & ~375 kJ/mol). MMPBSA, RMSD, and H-bond analysis support the notion that netrasudil interacts most effectively with the FDA compounds.

Conclusion

Our multi-tiered computational approach, evaluated as a whole, finds intriguing natural scaffolds for TrxR inhibition and provides an adequate basis for lead optimization in amoebosis treatment. Overall, Prior use of these compounds may be required for in-vitro and in-vivo evaluations.