Helminths, including cestodes, nematodes and trematodes, are a huge global health burden, infecting hundreds of millions of people. In many cases, existing drugs such as benzimidazoles, diethylcarbamazine, ivermectin and praziquantel are insufficiently efficacious, contraindicated in some populations, or at risk of the development of resistance, thereby impeding progress towards World Health Organization goals to control or eliminate these neglected tropical diseases. However, there has been limited recent progress in developing new drugs for these diseases due to lack of commercial attractiveness, leading to the introduction of novel, more efficient models for drug innovation that attempt to reduce the cost of research and development. Open science aims to achieve this by encouraging collaboration and the sharing of data and resources between organisations. In this review we discuss how open science has been applied to anthelmintic drug discovery. Open resources, including genomic information from many parasites, are enabling the identification of targets for new antiparasitic agents. Phenotypic screening remains important, and there has been much progress in open-source systems for compound screening with parasites, including motility assays but also high content assays with more detailed investigation of helminth physiology. Distributed open science compound screening programs, such as the Medicines for Malaria Venture Pathogen Box, have been successful at facilitating screening in diverse assays against many different parasite pathogens and models. Of the compounds identified so far in these screens, tolfenpyrad, a repurposed insecticide, shows significant promise and there has been much progress in creating more potent and selective derivatives. This work exemplifies how open science approaches can catalyse drug discovery against neglected diseases.

中文翻译：

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驱虫药物发现：靶点识别、筛选方法和开放科学的作用。


蠕虫，包括绦虫、线虫和吸虫，是一个巨大的全球健康负担，感染了数亿人。在许多情况下，苯并咪唑、二乙基卡马嗪、伊维菌素和吡喹酮等现有药物的疗效不够，对某些人群有禁忌，或者有产生耐药性的风险，从而阻碍了世界卫生组织控制或消除这些被忽视的热带病的目标的实现。然而，由于缺乏商业吸引力，最近在开发针对这些疾病的新药方面进展有限，导致引入新颖、更有效的药物创新模式，试图降低研发成本。开放科学旨在通过鼓励组织之间的合作以及数据和资源共享来实现这一目标。在这篇综述中，我们讨论了开放科学如何应用于驱虫药物的发现。开放资源，包括来自许多寄生虫的基因组信息，使得能够识别新的抗寄生虫药物的靶点。表型筛选仍然很重要，并且用于寄生虫化合物筛选的开源系统已经取得了很大进展，包括运动测定以及对蠕虫生理学进行更详细研究的高内涵测定。分布式开放科学化合物筛选项目，例如“疟疾风险病原体药物盒”，已经成功地促进了针对许多不同寄生虫病原体和模型的多种检测的筛选。迄今为止在这些筛选中鉴定的化合物中，吡虫酰胺（一种重新利用的杀虫剂）显示出巨大的前景，并且在创造更有效和选择性的衍生物方面已经取得了很大进展。 这项工作例证了开放科学方法如何促进针对被忽视疾病的药物发现。