Jin Yaqian, Sehgal Sheikh Arslan, Hassan Faizul, Liu Guiqin
Shandong Donkey Industry Technology Collaborative Innovation Center, College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China.
Department of Genomics and Bioinformatics, Faculty of Animal Production & Technology, Cholistan University of Veterinary & Animal Sciences, Bahawalpur 63100, Pakistan.
Animals (Basel). 2025 Jun 23;15(13):1846. doi: 10.3390/ani15131846.
Haemonchosis caused by the parasitic worm is a major threat to cattle and other ruminants and imposes significant economic losses in the livestock industry. Different medications have been reported; however, these are not reliable now due to mass drug resistance. The current study investigates potential inhibitors of two proteins: glutathione S-transferase (GST) and beta-tubulin isotype 1. GST helps the parasite to detoxify harmful substances, while beta-tubulin is essential for the cell division and structure. By using computational approaches, natural compounds were identified to inhibit the selected proteins. The 3D structures of GST and β-tubulin isotype 1 were prepared, and pharmacophore models were generated to search the Molport natural compound library. The lowest binding energy ranged from -6.7 to -10.4 Kcal/mol. Post-docking interactional analyses revealed that Glu45, Arg46, Cys126, Gln131, Lys252, Asn247, and Arg251 residues were the most common interacting residues in β-tubulin isotype 1. Similarly, in GST, Leu99, Asn100, Arg103, Lys107, Glu162, and Met163 were the most common interacting residues. In conclusion, extensive computational analyses including virtual screening, docking, and MD simulations revealed that the compound Molport-039-195-358 might have the ability to control haemonchosis by targeting GST and β-tubulin isotype 1. The in silico studies identified potent compounds by targeting GST and β-tubulin isotype 1 against . The reported findings provide a foundation for the development of novel anthelmintic therapies.
由寄生虫引起的捻转血矛线虫病对牛和其他反刍动物构成重大威胁，并给畜牧业带来巨大经济损失。已有不同药物被报道；然而，由于广泛的耐药性，这些药物目前已不可靠。当前研究调查了两种蛋白质的潜在抑制剂：谷胱甘肽S -转移酶（GST）和β -微管蛋白同种型1。GST帮助寄生虫解毒有害物质，而β -微管蛋白对于细胞分裂和结构至关重要。通过使用计算方法，鉴定出天然化合物可抑制所选蛋白质。制备了GST和β -微管蛋白同种型1的三维结构，并生成药效团模型以搜索Molport天然化合物库。最低结合能范围为 - 6.7至 - 10.4千卡/摩尔。对接后相互作用分析表明，Glu45、Arg46、Cys126、Gln131、Lys252、Asn247和Arg251残基是β -微管蛋白同种型1中最常见的相互作用残基。同样，在GST中，Leu99、Asn100、Arg103、Lys107、Glu162和Met163是最常见的相互作用残基。总之，包括虚拟筛选、对接和分子动力学模拟在内的广泛计算分析表明，化合物Molport - 039 - 195 - 358可能通过靶向GST和β -微管蛋白同种型1来控制捻转血矛线虫病。计算机模拟研究通过靶向GST和β -微管蛋白同种型1鉴定出了有效的化合物。所报道的研究结果为开发新型驱虫疗法奠定了基础。
