Meshram Rohan J, Goundge Mayuri B, Kolte Baban S, Gacche Rajesh N
Bioinformatics Centre, Savitribai Phule Pune University, Pune 411007, India.
Bioinformatics Centre, Savitribai Phule Pune University, Pune 411007, India.
Parasitol Int. 2019 Apr;69:59-70. doi: 10.1016/j.parint.2018.11.006. Epub 2018 Nov 29.
Leishmaniasis is one of the major health issue in developing countries. The current therapeutic regimen for this disease is less effective with lot of adverse effects thereby warranting an urgent need to develop not only new and selective drug candidates but also identification of effective drug targets. Here we present subtractive genomics procedure for identification of putative drug targets in Leishmania. Comprehensive druggability analysis has been carried out in the current work for identified metabolic pathways and drug targets. We also demonstrate effective metabolic simulation methodology to pinpoint putative drug targets in threonine biosynthesis pathway. Metabolic simulation data from the current study indicate that decreasing flux through homoserine kinase reaction can be considered as a good therapeutic opportunity. The data from current study is expected to show new avenue for designing experimental strategies in search of anti-leishmanial agents.
利什曼病是发展中国家的主要健康问题之一。目前针对该疾病的治疗方案效果欠佳且有诸多不良反应，因此迫切需要研发不仅新的且具选择性的候选药物，还要鉴定有效的药物靶点。在此，我们展示了用于鉴定利什曼原虫中假定药物靶点的消减基因组学方法。在当前工作中，已对鉴定出的代谢途径和药物靶点进行了全面的药物可及性分析。我们还展示了有效的代谢模拟方法，以确定苏氨酸生物合成途径中的假定药物靶点。当前研究的代谢模拟数据表明，降低高丝氨酸激酶反应的通量可被视为一个良好的治疗契机。预计当前研究的数据将为设计寻找抗利什曼病药物的实验策略开辟新途径。
