Fascioliasis, caused by trematode parasites of the Fasciola spp. remains a
significant global health concern, affecting both humans and livestock. This neglected
tropical disease, along with other food-borne trematodes, impacts over 10% of the
world's population, resulting in substantial economic losses exceeding $3 billion
annually in the livestock industry. Since no vaccine has been developed so far, current
disease control relies mainly on drugs, particularly triclabendazole, which although
effective, faces challenges due to reported resistance in many regions. With Fasciola
hepatica being the common fluke, its wide distribution and intricate life cycle,
emphasize the importance of understanding parasite epidemiology and biology and
addressing drug resistance. However, few efforts have been pursued in the last decade
to develop new drugs against fascioliasis. There are different approaches to drug
discovery. Screening methodologies may target essential parasite proteins through in
silico or in vitro studies, employing protein docking and molecular dynamic
simulations. This enables the rapid identification of potential drug candidates for
subsequent in vitro or in vivo testing. Alternatively, phenotypic screenings with
cultured parasites offer a broader understanding of drug efficacy but present challenges
in terms of automation and the unknown mode of action of the drug candidates. Also,
drug repurposing has emerged as a promising strategy in recent years. This approach
accelerates the drug development process, addressing the lengthy timelines typically
associated with bringing novel drugs to the market. This chapter provides a
comprehensive overview of drug discovery efforts in the last ten years for fascioliasis
treatment. In-depth discussions on drugs targeting specific F. hepatica molecular
components are presented followed by phenotypic screenings with synthetic and
natural compounds. The chapter concludes with a review of some scarce initiatives in
drug repurposing, providing an overview of the various strategies employed to address
drug discovery in fascioliasis.
Keywords: Anthelmintic, Cathepsin L, Drug development, Drug repurposing, Fasciola gigantica, Fasciola hepatica, Fascioliasis, Fasciolicide activity, Flukicidal activity, Foodborne trematode disease.
