PR002490 (Project)

Description:Trichinella spiralis is the parasitic nematodes that cause trichinellosis. Patients are infected with T. spiralis by consuming raw meat containing larval stage of the parasite. Patients may develop weakness, muscle pain, facial edema, or death in severe cases. Albendazole (ABZ) is the drug of choice for trichinellosis, however, the resistance to ABZ has been repeatedly reported. Hence, novel drugs against this parasite are essentially required. Developing new drugs is expensive and time-consuming. To overcome these limitations, the application of computational approaches and drug repurposing strategy would be a suitable solution. Here, we aimed to discover new anthelmintic drugs for T. spiralis using in silico-based techniques and in vitro validation. Firstly, we treated both adult and larval stages of T. spiralis with ABZ, then metabolome of the parasites were extracted. Following liquid chromatography-tandem mass spectrometry analysis, an approximately of 11,187-11,191 features were identified from XCMS online platform. From the metabolome data, there were 122 and 133 metabolites those were significantly changed by ABZ treatment in adult and larval stages, respectively. The pathway analysis was performed with Metaboanalyst platform and fatty acid degradation pathway was highlighted in both stages of the parasites. This pathway is vital for lipid metabolism of the worms, hence, we screened for potential drug targets in this pathway. We found that Carnitine palmitoyl transferase (CPT) 1 and 2 are the enzymes responsible for transporting fatty acids into mitochondria. Inhibiting these enzymes would shut down the lipid metabolism machinery of the parasites. Hence, these enzymes were proposed as the potential drug targets for trichinellosis treatment in the future.