Biomolecules Discovery Group, Universidad Regional Amazónica Ikiam, Tena 150150, Ecuador.
LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, P-4169-007 Porto, Portugal.
Int J Biol Macromol. 2023 Jul 1;242(Pt 2):124745. doi: 10.1016/j.ijbiomac.2023.124745. Epub 2023 May 6.
Malaria, leishmaniasis and Chagas disease are vector-borne protozoal infections with a disproportionately high impact on the most fragile societies in the world, and despite malaria-focused research gained momentum in the past two decades, both trypanosomiases and leishmaniases remain neglected tropical diseases. Affordable effective drugs remain the mainstay of tackling this burden, but toxicicty, inneficiency against later stage disease, and drug resistance issues are serious shortcomings. One strategy to overcome these hurdles is to get new therapeutics or inspiration in nature. Indeed, snake venoms have been recognized as valuable sources of biomacromolecules, like peptides and proteins, with antiprotozoal activity. This review highlights major snake venom components active against at least one of the three aforementioned diseases, which include phospholipases A2, metalloproteases, L-amino acid oxidases, lectins, and oligopeptides. The relevance of this repertoire of biomacromolecules and the bottlenecks in their clinical translation are discussed considering approaches that should increase the success rate in this arduous task. Overall, this review underlines how venom-derived biomacromolecules could lead to pioneering antiprotozoal treatments and how the drug landscape for neglected diseases may be revolutionized by a closer look at venoms. Further investigations on poorly studied venoms is needed and could add new therapeutics to the pipeline.
疟疾、利什曼病和恰加斯病是由媒介传播的原生动物感染，对世界上最脆弱的社会造成了不成比例的巨大影响。尽管过去二十年疟疾相关研究进展迅速，但锥虫病和利什曼病仍然是被忽视的热带病。负担得起的有效药物仍然是应对这一负担的主要手段，但毒性、对后期疾病的低效性和耐药性问题仍然严重。克服这些障碍的一种策略是从自然界中获得新的治疗方法或灵感。事实上，蛇毒已被公认为具有抗原生动物活性的生物大分子（如肽和蛋白质）的有价值来源。本综述重点介绍了至少对上述三种疾病中的一种具有活性的主要蛇毒成分，包括磷脂酶 A2、金属蛋白酶、L-氨基酸氧化酶、凝集素和寡肽。考虑到应该提高这项艰巨任务的成功率的方法，讨论了这些生物大分子的相关性及其在临床转化中的瓶颈。总的来说，本综述强调了毒液衍生的生物大分子如何为开拓性的抗原生动物治疗提供可能，以及通过更深入地研究毒液，可能会彻底改变被忽视疾病的药物治疗前景。需要对研究较少的毒液进行进一步研究，这可能会为药物研发提供新的方法。
