Structure-Based Identification of Selective Phytochemical Inhibitors Targeting EmCoASY: A Novel Therapeutic Strategy Against Alveolar Echinococcosis | ||
| Zagazig University Medical Journal | ||
| Volume 31, Issue 9, September 2025, Pages 4420-4440 PDF (1.39 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/zumj.2025.392468.3991 | ||
| Author | ||
| Abdulbaset Mohammad M Kabli* | ||
| Department of Laboratory Medicine , Faculty of Applied Medical Sciences Al-Baha University, Al-Baha, Kingdom of Saudi Arabia | ||
| Abstract | ||
| Abstract Background: Alveolar echinococcosis (AE), caused by the larval stage of Echinococcus multilocularis, is a life-threatening zoonotic disease with limited treatment options due to chemotherapy-associated toxicity and incomplete parasitic clearance. The aim of this study was to identify selective phytochemical inhibitors targeting dephospho-CoA synthase (EmCoASY), a critical enzyme for parasite survival, using a structure-based drug discovery approach. Methods: A total of 419 phytochemicals with reported antiparasitic or antimalarial activity were collected from literature and databases. After structure retrieval from PubChem, 297 compounds were subjected to ADMET screening using SwissADME and pkCSM tools. Toxicity-based filtering shortlisted 20 compounds. These were docked against EmCoASY and its human homolog (HsCoASY) to assess binding affinity and selectivity. Top candidates underwent 200 ns molecular dynamics (MD) simulations, including RMSD, RMSF, principal component, covariance matrix, and hydrophobic surface analyses. MM/GBSA calculations were performed to estimate binding free energies. Results: Chaparrinone (CID: 73154) and artesunate (CID: 6917864) showed strong binding affinities (-8.9 and -8.2 kcal/mol) to EmCoASY with minimal interaction with HsCoASY. Molecular dynamics simulations revealed stable protein-ligand complexes with reduced conformational fluctuations. MM/GBSA analysis indicated that chaparrinone had the most favorable binding energy (-71.68 kcal/mol), driven by ΔG bind and lipophilic interactions. Conclusion: This structure-based in silico study identifies chaparrinone and artesunate as promising selective inhibitors of EmCoASY. Their favorable selectivity, stability, and binding energetics support their potential as novel therapeutic agents for alveolar echinococcosis. Further in vitro and in vivo validation studies are recommended to confirm their efficacy and safety. | ||
| Keywords | ||
| alveolar echinococcosis; Echinococcus multilocularis; dephospho-CoA synthase; molecular docking simulation; phytochemical | ||
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