Laboratorio de Microbiología y Biología Molecular, Programa de Medicina, Corporación Universitaria Empresarial Alexander von Humboldt, Armenia, Colombia.
Grupo de Estudio en Parasitología Molecular, Centro de Investigaciones Biomédicas, Universidad del Quindío, Armenia, Colombia.
Front Cell Infect Microbiol. 2019 Jan 7;8:439. doi: 10.3389/fcimb.2018.00439. eCollection 2018.
There is an urgent need to develop new treatments for Chagas' disease. To identify drug targets, it is important to understand the basic biology of , in particular with respect to the biological pathways or proteins that are essential for its survival within the host. This review provides a streamlined approach for identifying drug targets using freely available chemogenetic databases and outlines the relevant characteristics of an ideal chemotherapeutic target. Among those are their essentiality, druggability, availability of structural information, and selectivity. At the moment only 16 genes have been found as essential by gene disruption in . At the TDR Targets database, a chemogenomics resource for neglected diseases, information about published structures for these genes was only found for three of these genes, and annotation of validated inhibitors was found in two. These inhibitors have activity against the parasitic stages present in the host. We then analyzed three of the pathways that are considered promising in the search for new targets: (1) Ergosterol biosynthesis, (2) Resistance to oxidative stress, (3) Synthesis of surface glycoconjugates. We have annotated all the genes that participate in them, identified those that are considered as druggable, and incorporated evidence from either spp. that supports the hypothesis that these pathways are essential for survival.
目前，仅有 16 个基因通过基因敲除被发现对 是必需的。在 TDR 目标数据库中，一个被忽视疾病的化学生物基因组学资源，仅为其中的 3 个基因找到了已发表结构的信息，而在 2 个基因中找到了已验证抑制剂的注释。这些抑制剂对存在于宿主体内的寄生虫阶段具有活性。然后，我们分析了在寻找新靶点时被认为有前途的三个途径：（1）麦角固醇生物合成，（2）抵抗氧化应激，（3）表面糖缀合物的合成。我们已经注释了所有参与这些途径的基因，确定了那些被认为具有成药性的基因，并从 spp. 中加入了支持这些途径对 生存至关重要的假说的证据。
