Structure-Based Virtual Screening of Potential Inhibitors Targeting the Prolyl-tRNA Synthetase (PRS) in: Insights from Molecular Docking, ADMET Studies, and Molecular Dynamics Simulations.

Abstract

Avian coccidiosis, caused by protozoan parasites of the genus, poses a major threat to the poultry industry worldwide, leading to severe economic losses through reduced growth rates, poor feed efficiency, and increased mortality. Although the conventional management of this disease has relied on anticoccidial drugs, the overwhelming use of these agents has led to the rapid emergence and spread of drug-resistantisolates, highlighting the urgent need for novel therapeutic approaches. This study employed computational approaches to identify novel inhibitors targetingprolyl-tRNA synthetase (EtPRS). Based on the virtual screening of a library of 3045 natural compounds, 42 high-confidence inhibitors were identified. Three compounds, including Chelidonine, Bicuculline, and Guggulsterone, demonstrated strong and selective binding to EtPRS through stable interactions within the active site. ADMET predictions revealed favorable safety profiles, while molecular dynamic simulations confirmed binding stability. Overall, this research established a solid framework for the development of effective anticoccidial agents targeting PRS, contributing to the advancement of therapeutic strategies for combating parasitic infections in the poultry industry.