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药物发现技术:秀丽隐杆线虫作为抗蠕虫治疗的模型。

Drug discovery technologies: Caenorhabditis elegans as a model for anthelmintic therapeutics.

机构信息

Departamento de Ciencias Biomédicas, Facultad de Veterinaria, Universidad de León, León, Spain.

Instituto de Ganadería de Montaña (CSIC-Universidad de León), León, Spain.

出版信息

Med Res Rev. 2020 Sep;40(5):1715-1753. doi: 10.1002/med.21668. Epub 2020 Mar 13.

DOI:10.1002/med.21668
PMID:32166776
Abstract

Helminthiasis is one of the gravest problems worldwide. There is a growing concern on less available anthelmintics and the emergence of resistance creating a major threat to human and livestock health resources. Novel and broad-spectrum anthelmintics are urgently needed. The free-living nematode Caenorhabditis elegans could address this issue through automated high-throughput technologies for the screening of large chemical libraries. This review discusses the strong advantages and limitations for using C elegans as a screening method for anthelmintic drug discovery. C elegans is the best model available for the validation of novel effective drugs in treating most, if not all, helminth infections, and for the elucidation the mode of action of anthelmintic candidates. This review also focuses on available technologies in the discovery of anthelmintics published over the last 15 years with particular attention to high-throughput technologies over conventional screens. On the other hand, this review highlights how combinatorial and nanomedicine strategies could prolong the use of anthelmintics and control resistance problems.

摘要

寄生虫病是全球最严重的问题之一。驱虫药的可用性越来越少,耐药性的出现对人类和牲畜健康资源构成了重大威胁,人们对此越来越关注。因此,我们迫切需要新型广谱驱虫药。自由生活的线虫秀丽隐杆线虫可以通过自动化高通量技术筛选大型化学文库来解决这个问题。本文讨论了将秀丽隐杆线虫作为筛选抗寄生虫药物的方法的主要优点和局限性。秀丽隐杆线虫是验证新型有效药物治疗大多数(如果不是全部)寄生虫感染的最佳模型,也是阐明候选驱虫药作用模式的最佳模型。本文还重点介绍了过去 15 年中在驱虫药发现方面的可用技术,特别关注高通量技术对传统筛选的优势。另一方面,本文还强调了组合和纳米医学策略如何延长驱虫药的使用时间并控制耐药性问题。

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