Rivara-Espasandín Martin, Palumbo Miranda Clara, Sosa Ezequiel J, Radío Santiago, Turjanski Adrián G, Sotelo-Silveira José, Fernandez Do Porto Dario, Smircich Pablo
Departamento de Genómica, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
Departamento de Genética, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Front Pharmacol. 2023 Apr 6;14:1136321. doi: 10.3389/fphar.2023.1136321. eCollection 2023.
, , and , commonly referred to as TriTryps, are a group of protozoan parasites that cause important human diseases affecting millions of people belonging to the most vulnerable populations worldwide. Current treatments have limited efficiencies and can cause serious side effects, so there is an urgent need to develop new control strategies. Presently, the identification and prioritization of appropriate targets can be aided by integrative genomic and computational approaches. In this work, we conducted a genome-wide multidimensional data integration strategy to prioritize drug targets. We included genomic, transcriptomic, metabolic, and protein structural data sources, to delineate candidate proteins with relevant features for target selection in drug development. Our final ranked list includes proteins shared by TriTryps and covers a range of biological functions including essential proteins for parasite survival or growth, oxidative stress-related enzymes, virulence factors, and proteins that are exclusive to these parasites. Our strategy found previously described candidates, which validates our approach as well as new proteins that can be attractive targets to consider during the initial steps of drug discovery.
锥虫属（Trypanosoma）、布氏锥虫（T. brucei）和枯氏锥虫（T. cruzi），通常被称为“三锥虫”（TriTryps），是一类原生动物寄生虫，可引发重要的人类疾病，影响着全球数百万最弱势群体。目前的治疗方法效率有限，且会导致严重的副作用，因此迫切需要开发新的控制策略。目前，整合基因组学和计算方法有助于识别合适的靶点并确定其优先级。在这项工作中，我们实施了一种全基因组范围的多维数据整合策略，以确定药物靶点的优先级。我们纳入了基因组、转录组、代谢组和蛋白质结构数据源，以描绘出具有相关特征的候选蛋白质，用于药物开发中的靶点选择。我们最终的排名列表包括三锥虫共有的蛋白质，涵盖了一系列生物学功能，包括寄生虫生存或生长所必需的蛋白质、氧化应激相关酶、毒力因子以及这些寄生虫特有的蛋白质。我们的策略发现了先前描述的候选靶点，这验证了我们的方法，同时也发现了新的蛋白质，这些蛋白质可能是药物发现初始阶段值得考虑的有吸引力的靶点。
