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分析原生动物感染的潜在药物靶点。

Analysis of Potential Drug Targets for Protozoan Infections.

机构信息

Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa, México.

ICMAT-CSIC, Madrid, Spain.

出版信息

Med Chem. 2022;19(1):91-98. doi: 10.2174/1573406418666220816121912.

Abstract

BACKGROUND

Currently, protozoan infectious diseases affect billions of people every year. Their pharmacological treatments offer few alternatives and are restrictive due to undesirable side effects and parasite drug resistance.

OBJECTIVE

In this work, three ontology-based approaches were used to identify shared potential drug targets in five species of protozoa.

METHODS

In this study, proteomes of five species of protozoa: Entamoeba histolytica (E. histolytica), Giardia lamblia (G. lamblia), Trichomonas vaginalis (T. vaginalis), Trypanosoma cruzi (T. cruzi), and Leishmania mexicana (L. mexicana), were compared through orthology inference using three different tools to identify potential drug targets.

RESULTS

Comparing the proteomes of E. histolytica, G. lamblia, T. vaginalis, T. cruzi, and L. mexicana, twelve targets for developing new drugs with antiprotozoal activity were identified.

CONCLUSION

New drug targets were identified by orthology-based analysis; therefore, they could be considered for the development of new broad-spectrum antiprotozoal drugs. Particularly, triosephosphate isomerase emerges as a common target in trypanosomatids and amitochondriate parasites.

摘要

背景

目前,原生动物传染病每年影响数十亿人。由于不良副作用和寄生虫耐药性,它们的药物治疗选择有限。

目的

在这项工作中,使用了三种基于本体的方法来鉴定五种原生动物中的共同潜在药物靶点。

方法

在这项研究中,通过使用三种不同的工具进行同源性推断,比较了五种原生动物的蛋白质组:溶组织内阿米巴(E. histolytica)、蓝氏贾第鞭毛虫(G. lamblia)、阴道毛滴虫(T. vaginalis)、克氏锥虫(T. cruzi)和墨西哥利什曼原虫(L. mexicana),以鉴定潜在的药物靶点。

结果

通过比较 E. histolytica、G. lamblia、T. vaginalis、T. cruzi 和 L. mexicana 的蛋白质组,鉴定了 12 个具有抗原生动物活性的新药靶点。

结论

通过基于同源性的分析鉴定了新的药物靶点,因此可以考虑开发新的广谱抗原生动物药物。特别是磷酸丙糖异构酶在原生动物和无线粒体寄生虫中是一个共同的靶点。

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