Discovery of Potential Anthelmintic Agents Against Gyrodactylus kobayashii Through Computer-Aided Drug Design and In Vivo Evaluation
文献类型： 外文期刊
作者： Dong, Jing 1 ; Xia, Liwei 2 ; Liu, Yongtao 1 ; Yang, Qiuhong 1 ; Xu, Ning 1 ; Ai, Xiaohui 1 ; Zhou, Shun 1 ;
作者机构： 1.Chinese Acad Fishery Sci, Yangtze River Fisheries Res Inst, Wuhan, Peoples R China
2.Tarim Univ, Coll Life Sci & Technol, Tarim Res Ctr Rare Fishes, Alar, Peoples R China
关键词： computer-aided drug design; Gyrodactylus kobayashii; monogenean; beta-Tubulin
期刊名称：JOURNAL OF FISH DISEASES （ 影响因子：2.2； 五年影响因子：2.2 ）
ISSN： 0140-7775
年卷期： 2025 年 48 卷 6 期
页码：
收录情况： SCI
摘要： Monogeneans are ectoparasitic flatworms causing significant economic losses in aquaculture. This study aimed to identify potential anthelmintic agents against these parasites by integrating computer-aided drug design (CADD) and in vivo evaluation. The beta-tubulin gene, a well-established anthelmintic target, was cloned from Gyrodactylus kobayashii and its three-dimensional structure was generated using homology modelling. Virtual screening of 2319 FDA-approved drugs and nine common benzimidazoles against the modelled beta-tubulin identified several promising compounds with low binding energy. Subsequent in vivo anthelmintic efficacy and acute toxicity assays in goldfish revealed etravirine as a potent candidate with an EC50 value of 0.55 mg/L and a therapeutic index (TI) greater than 18.18. This favourable safety profile highlights etravirine's potential for controlling monogenean infections in aquaculture. Flubendazole and mebendazole also demonstrated potent anthelmintic activity, with EC50 values of 0.022 and 0.023 mg/L and therapeutic indices exceeding 45.45 and 43.48, respectively. Molecular dynamics simulations confirmed stable binding modes for flubendazole and mebendazole with beta-tubulin, providing mechanistic insights into their anthelmintic activity. Overall, this study demonstrated the utility of CADD in identifying potential therapeutic agents against monogenean and underscored the importance of beta-tubulin as a key target for anthelmintic therapy, contributing to the development of sustainable aquaculture practices.
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