Abstract

--- - Purpose Fasciola hepatica is a globally distributed trematode that causes significant economic losses. Triclabendazole is the primary pharmacological treatment for this parasite. However, the increasing resistance to triclabendazole limits its efficacy. Previous pharmacodynamics studies suggested that triclabendazole acts by interacting mainly with the ss monomer of tubulin. - Methods We used a high-quality method to model the six isotypes of F. hepatica ss-tubulin in the absence of three-dimensional structures. Molecular dockings were conducted to evaluate the destabilization regions in the molecule against the ligands triclabendazole, triclabendazole sulphoxide and triclabendazole sulphone. - Results The nucleotide binding site demonstrates higher affinity than the binding sites of colchicine, albendazole, the T7 loop and p ss VII (p < 0.05). We suggest that the binding of the ligands to the polymerization site of ss-tubulin can lead a microtubule disruption. Furthermore, we found that triclabendazole sulphone exhibited significantly higher binding affinity than other ligands (p < 0.05) across all isotypes of ss-tubulin. - Conclusions Our investigation has yielded new insight on the mechanism of action of triclabendazole and its sulphometabolites on F. hepatica ss-tubulin through computational tools. These findings have significant implications for ongoing scientific research ongoing towards the discovery of novel therapeutics to treat F. hepatica infections.