Antiechinococcal assessment of atovaquone—an in silico and in vitro analysis

Cystic echinococcosis (CE), a hydatid disease, caused by larval form of dog tapeworm Echiconoccus granulosus, is responsible for considerable human morbidity and mortality. The currently available drugs have to be applied in high doses for prolonged periods for treatment of CE, and have several side effects. Atovaquone, a naphthoquinone, has previously been shown to possess a very promising antiparasitic potential against malaria, toxoplasmosis, babesiasis, etc. by inhibiting parasite’s electron transport chain, cytochrome bc1 complex. Thus, the present study was aimed to investigate the antiechinococcal potency of atovaquone. The mode of binding of atovaquone to cytochrome bc1 complex of E. granulosus was also predicted using in silico approach. The 3D model of cytbc1 complex of E. granulosus was prepared using I-Tasser server and was docked with atovaquone. The docking results predicted the binding of atovaquone to Thr-371 amino acid of Ubiquinol region of cyt b. The protoscolicidal efficacy of atovaquone was further investigated by in vitro experiments. Dose-dependent death of protoscolesces was observed within a few time intervals after treatment with atovaquone, thereby indicating its potential in treatment of CE. The 100% protoscolicidal activity of atovaquone was achieved at a concentration of 20 μg/mL within 60 h of treatment. It is probably the first study to investigate the effect of atovaquone on protoscolesces of E. granulosus. The results of the present study are quite encouraging indicating the potential for atovaquone as an alternative treatment option against CE. It should further be tested in combination with other currently available chemotherapeutic drugs for the treatment of CE.