SCREENING OF ANTIPARASITIC COMPOUNDS FOR THYMIDYLATE SYNTHASE FROM TRICHINELLA SPIRALIS: EXTENSIVE VIRTUAL SCREENING AND MOLECULAR MODELING STUDIES

Lakshminarayanan Karthik* and Ummu Kulsu T. S.

ABSTRACT

Trichinella spiralis (T. spiralis), a parasitic nematode responsible for human trichinellosis, poses a significant threat to global health. Thymidylate synthase (TS) plays a crucial role in DNA synthesis and repair, making it an attractive target for drug development against this parasite. In this context, the present study aimed to identify potential small-molecule TS inhibitors in T. spiralis and evaluate their binding affinity through docking studies. To achieve this goal, we first conducted a comprehensive screening of chemical libraries to identify potential TS inhibitors using several small-molecule databases. Subsequently, we performed extensive docking studies to investigate the binding interactions between these compounds and the active site of TS, providing insights into their potential mechanisms of action. Our findings highlight several promising small molecules that exhibit high binding energy and strong binding affinities toward T. spiralis TS, suggesting their potential as novel therapeutic agents against trichinellosis. Furthermore, a comprehensive analysis of physicochemical and pharmacokinetic properties was also performed for the identified hits from each library. Ultimately, this study contributes to ongoing efforts to combat T. spiralis infections and underscores the importance of targeting essential enzymes such as TS as a strategy for parasite control.

Keywords: Virtual screening docking; ADMET analysis; Trichinella spiralis; Thymidylate synthase; Rheediaxanthone B; PyRx docking.