Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Proteomics Unit, Cancer Research Centre (IBMCC/CSIC/USAL/IBSAL), 37007, Salamanca, Spain.
Pathog Dis. 2021 Jan 9;79(1). doi: 10.1093/femspd/ftaa071.
There is no effective vaccine against malaria; therefore, chemotherapy is to date the only choice to fight against this infectious disease. However, there is growing evidences of drug-resistance mechanisms in malaria treatments. Therefore, the identification of new drug targets is an urgent need for the clinical management of the disease. Proteomic approaches offer the chance of determining the effects of antimalarial drugs on the proteome of Plasmodium parasites. Accordingly, we reviewed the effects of antimalarial drugs on the Plasmodium falciparum proteome pointing out the relevance of several proteins as possible drug targets in malaria treatment. In addition, some of the P. falciparum stage-specific altered proteins and parasite-host interactions might play important roles in pathogenicity, survival, invasion and metabolic pathways and thus serve as potential sources of drug targets. In this review, we have identified several proteins, including thioredoxin reductase, helicases, peptidyl-prolyl cis-trans isomerase, endoplasmic reticulum-resident calcium-binding protein, choline/ethanolamine phosphotransferase, purine nucleoside phosphorylase, apical membrane antigen 1, glutamate dehydrogenase, hypoxanthine guanine phosphoribosyl transferase, heat shock protein 70x, knob-associated histidine-rich protein and erythrocyte membrane protein 1, as promising antimalarial drugs targets. Overall, proteomic approaches are able to partially facilitate finding possible drug targets. However, the integration of other 'omics' and specific pharmaceutical techniques with proteomics may increase the therapeutic properties of the critical proteins identified in the P. falciparum proteome.
目前尚无有效的疟疾疫苗；因此，到目前为止，化疗是对抗这种传染病的唯一选择。然而，疟疾治疗中耐药机制的证据越来越多。因此，确定新的药物靶点是临床治疗这种疾病的迫切需要。蛋白质组学方法提供了确定抗疟药物对疟原虫蛋白质组影响的机会。因此，我们综述了抗疟药物对恶性疟原虫蛋白质组的影响，指出了几种蛋白质作为疟疾治疗中可能的药物靶点的相关性。此外，疟原虫阶段特异性改变的蛋白质和寄生虫-宿主相互作用中的一些可能在致病性、生存、入侵和代谢途径中发挥重要作用，因此可能成为潜在的药物靶点来源。在这篇综述中，我们确定了几种蛋白质，包括硫氧还蛋白还原酶、解旋酶、肽基脯氨酰顺反异构酶、内质网驻留钙结合蛋白、胆碱/乙醇胺磷酸转移酶、嘌呤核苷磷酸化酶、顶膜抗原 1、谷氨酸脱氢酶、次黄嘌呤鸟嘌呤磷酸核糖转移酶、热休克蛋白 70x、 knob 相关组氨酸丰富蛋白和红细胞膜蛋白 1，作为有前途的抗疟药物靶点。总的来说，蛋白质组学方法能够部分促进寻找可能的药物靶点。然而，将其他“组学”和特定的药物技术与蛋白质组学相结合，可能会增加在恶性疟原虫蛋白质组中鉴定出的关键蛋白质的治疗特性。
