Ivermectin Identified Using a High-Throughput Screening System Exhibits Anti- Activity in Rats.

Clonorchiasis, caused by the parasite , remains a public health concern in East Asian countries. In this study, high-throughput screening was used to analyze 320 compounds for potential inhibitory activity against . To ensure the selection of high-confidence hits, a stringent inhibition threshold of 80% was applied, leading to the identification of three active compounds: moxifloxacin, hexachlorophene, and ivermectin (IVM). Ivermectin emerged as a hit compound and was assessed for its anti- efficacy. Ivermectin demonstrated dose-dependent trematocidal activity against metacercariae (CsMC) and newly excysted juveniles (CsNEJs), showing superior efficacy against CsMC and CsNEJs compared to praziquantel. To assess in vivo efficacy, rats were infected with CsMC and treated with ivermectin at 1 and 4 weeks post-infection (wpi) to target larval and adult stages, respectively. A significant worm burden reduction was observed compared to untreated control when treatment was administered at 1 wpi, showing an antiparasitic effect against larvae. Parasite-specific IgG levels and ALT/AST responses were comparable to those of the infection control group. These findings suggest that ivermectin may serve as a potential alternative drug targeting larvae.