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Background <p>Anti-enteroviral denotes agents intended to prevent or treat infections caused by enteroviruses a broad class of viruses including poliovirus, coxsackieviruses and rhinovirus that are responsible for diseases ranging from mild respiratory illnesses to severe clinical conditions. At present, there are no approved virus-specific therapies for enteroviral infections. The present study emphasizes a molecular modeling investigation of Pleconaril derivatives to identify promising lead compounds for the treatment of enteroviral infections. The ligand library that was responsible for reporting the anti-enteroviral activities was derived from the literature that contained twenty four novel pleconaril derivatives.</p> Methods <p>To design future analogs of the novel pleconaril derivatives, research was done to develop the Atom-based and Field-based-3D QSAR (Quantitative structure-activity relationship models) models. PHASE was utilized for generating a common pharmacophore and conducting 3D-QSAR studies. The protein target (PDB ID: 4WM7) was chosen, and docking was performed to identify optimal binding modes between the target and ligands. EV-D68’s crystal structure and its complex with pleconaril (PDB ID: 4WM7) had 2.32 Å resolution. The free energy was calculated using PRIME-Molecular Mechanics with Generalized Born and Surface Area Solvation (MM/GBSA). Molecular properties and ADME parameters were assessed with the QikProp utility and SwissADME.</p> Results <p>In the docking study, molecule 12b had a docking score of -12.210&#xa0;kcal/mol and was most closely aligned with 4WM7. Compared to Pleconaril (-11.466&#xa0;kcal/mol), a natural ligand, it was more effectively docked. All compounds, with the exception of a small number, had values that fell within a reasonable range. The rule of five values fell within the acceptable range. We chose the top-ranked six-point hypothesis, AHHRRR_1. All active compounds were correlated with the developed best-ranking hypothesis by aligning them on the chosen pharmacophore AHHRRR_1.</p> Conclusion <p>In conclusion, 3D-QSAR models, and free energy were calculated, ADME parameters were assessed, and a comparative docking study of the pleconaril derivatives against the enterovirus target.</p>

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Molecular modelling studies on novel pleconaril derivatives as antienteroviral agents

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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  • Chetan Palvi,
  • Snehal Ukhade,
  • Isha S. Ingle,
  • Sanchali S. Gadade,
  • Hemchandra K. Chaudhari

摘要

Background

Anti-enteroviral denotes agents intended to prevent or treat infections caused by enteroviruses a broad class of viruses including poliovirus, coxsackieviruses and rhinovirus that are responsible for diseases ranging from mild respiratory illnesses to severe clinical conditions. At present, there are no approved virus-specific therapies for enteroviral infections. The present study emphasizes a molecular modeling investigation of Pleconaril derivatives to identify promising lead compounds for the treatment of enteroviral infections. The ligand library that was responsible for reporting the anti-enteroviral activities was derived from the literature that contained twenty four novel pleconaril derivatives.

Methods

To design future analogs of the novel pleconaril derivatives, research was done to develop the Atom-based and Field-based-3D QSAR (Quantitative structure-activity relationship models) models. PHASE was utilized for generating a common pharmacophore and conducting 3D-QSAR studies. The protein target (PDB ID: 4WM7) was chosen, and docking was performed to identify optimal binding modes between the target and ligands. EV-D68’s crystal structure and its complex with pleconaril (PDB ID: 4WM7) had 2.32 Å resolution. The free energy was calculated using PRIME-Molecular Mechanics with Generalized Born and Surface Area Solvation (MM/GBSA). Molecular properties and ADME parameters were assessed with the QikProp utility and SwissADME.

Results

In the docking study, molecule 12b had a docking score of -12.210 kcal/mol and was most closely aligned with 4WM7. Compared to Pleconaril (-11.466 kcal/mol), a natural ligand, it was more effectively docked. All compounds, with the exception of a small number, had values that fell within a reasonable range. The rule of five values fell within the acceptable range. We chose the top-ranked six-point hypothesis, AHHRRR_1. All active compounds were correlated with the developed best-ranking hypothesis by aligning them on the chosen pharmacophore AHHRRR_1.

Conclusion

In conclusion, 3D-QSAR models, and free energy were calculated, ADME parameters were assessed, and a comparative docking study of the pleconaril derivatives against the enterovirus target.