Kamal Muntasir, Mukherjee Suprabhat, Joshi Bishnu, Sindhu Zia-Ud-Din, Wangchuk Phurpa, Haider Shawkat, Ahmed Nurnabi, Talukder Md Hasanuzzaman, Geary Timothy G, Yadav Arun K
Department of Molecular Genetics, University of Toronto, Toronto, Canada.
Department of Animal Science, Kazi Nazrul University, Asansol 713340, West Bengal, India.
Mol Biochem Parasitol. 2023 Dec;256:111594. doi: 10.1016/j.molbiopara.2023.111594. Epub 2023 Sep 18.
With the increasing prevalence of anthelmintic resistance in animals recorded globally, and the threat of resistance in human helminths, the need for novel anthelmintic drugs is greater than ever. Most research aimed at discovering novel anthelmintic leads relies on high throughput screening (HTS) of large libraries of synthetic small molecules in industrial and academic settings in developed countries, even though it is the tropical countries that are most plagued by helminth infections. Tropical countries, however, have the advantage of possessing a rich flora that may yield natural products (NP) with promising anthelmintic activity. Focusing on South Asia, which produces one of the world's highest research outputs in NP and NP-based anthelmintic discovery, we find that limited basic research and funding, a lack of awareness of the utility of model organisms, poor industry-academia partnerships and lack of technological innovations greatly limit anthelmintics research in the region. Here we propose that utilizing model organisms including the free-living nematode Caenorhabditis elegans, that can potentially allow rapid target identification of novel anthelmintics, and Oscheius tipulae, a closely related, free-living nematode which is found abundantly in soil in hotter temperatures, could be a much-needed innovation that can enable cost-effective and efficient HTS of NPs for discovering compounds with anthelmintic/antiparasitic potential in South Asia and other tropical regions that historically have devoted limited funding for such research. Additionally, increased collaborations at the national, regional and international level between parasitologists and pharmacologists/ethnobotanists, setting up government-industry-academia partnerships to fund academic research, creating a centralized, regional collection of plant extracts or purified NPs as a dereplication strategy and HTS library, and holding regional C. elegans/O. tipulae-based anthelmintics workshops and conferences to share knowledge and resources regarding model organisms may collectively promote and foster a NP-based anthelmintics landscape in South Asia and beyond.
随着全球记录的动物体内抗蠕虫药耐药性日益普遍，以及人类蠕虫产生耐药性的威胁，对新型抗蠕虫药的需求比以往任何时候都更加迫切。尽管热带国家受蠕虫感染困扰最为严重，但大多数旨在发现新型抗蠕虫药先导物的研究依赖于发达国家工业和学术机构对大型合成小分子文库进行的高通量筛选（HTS）。然而，热带国家拥有丰富的植物群，有可能从中产生具有潜在抗蠕虫活性的天然产物（NP）。以南亚为例，该地区在NP及基于NP的抗蠕虫药发现方面的研究产出位居世界前列，但我们发现，基础研究和资金有限、对模式生物效用缺乏认识、产学研合作不佳以及缺乏技术创新，极大地限制了该地区的抗蠕虫药研究。在此，我们建议利用包括自由生活线虫秀丽隐杆线虫在内的模式生物，它有可能实现新型抗蠕虫药的快速靶点鉴定；还有奥氏尖尾线虫，这是一种密切相关的自由生活线虫，在温度较高的土壤中大量存在。这可能是一项急需的创新，能够以具有成本效益且高效的方式对NP进行高通量筛选，以便在南亚和其他历史上对此类研究投入资金有限的热带地区发现具有抗蠕虫/抗寄生虫潜力的化合物。此外，寄生虫学家与药理学家/民族植物学家之间在国家、区域和国际层面加强合作，建立政府-产业-学术界合作伙伴关系以资助学术研究，创建一个集中的、区域性的植物提取物或纯化NP集合作为去重复策略和高通量筛选文库，并举办基于秀丽隐杆线虫/奥氏尖尾线虫的区域性抗蠕虫药研讨会和会议，以分享有关模式生物的知识和资源，这些举措可能共同促进并推动南亚及其他地区基于NP的抗蠕虫药发展态势。
