مسار بولونيا
EN

صباح نوري حمادي ذياب النعيمي

السنة عنوان البحث نشر البحث
2026 Comparative Computational Screening of Antiviral Compounds Targeting Fish Cyprinid Herpesvirus-3 and Human HSV-1 Thymidine Kinases Egyptian Journal of Aquatic Biology & Fisheries
Thymidine kinase (TK) is a key enzyme in viral DNA replication and an important therapeutic target in herpesvirus infections affecting both fish and humans. The present study used a comparative computational screening approach to identify potential antiviral compounds targeting the thymidine kinases of human herpes simplex virus type 1 (HSV-1) and the fish pathogen Cyprinid herpesvirus-3 (CyHV-3). For both viral TK proteins, 145,853 small molecules were virtually screened by molecular docking, followed by molecular dynamics simulations, MM/GBSA binding free-energy calculations, and ADMET profiling to evaluate binding stability and predicted pharmacokinetic properties. Several compounds showed strong predicted affinity for both targets, favorable docking scores, and interactions with key catalytic residues. Comparative docking revealed differences in ligand affinity and binding modes between HSV-1 TK and CyHV-3 TK, consistent with structural differences in their active sites. The 100 ns MD simulations further showed stable binding of the Ligand 2-protein complex, with low RMSD fluctuations and persistent hydrogen-bond interactions involving GLN125, ARG222, and TYR101. MM/GBSA analysis identified Ligand 2 as having the most favorable binding free energy among the screened compounds and the reference co-crystal ligand. ADMET prediction also indicated acceptable drug- likeness, bioavailability, and low predicted toxicity risk for Ligand 2, whereas some screened ligands showed potential hepatotoxicity and hERG-related liabilities. Overall, the findings identify Ligand 2 as a promising broad-spectrum antiviral candidate for further investigation against both human and fish herpesviruses and provide a computational basis for subsequent experimental validation.