In silico REPOSITIONING OF NEW DRUGS AGAINST Schistosoma mansoni
In silico REPOSITIONING OF NEW DRUGS AGAINST Schistosoma mansoni
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DOI：
10.5216/rpt.v47i3.55429
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发表时间：
2018-07-01
期刊：
影响因子：
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通讯作者：
Neves Junior, Bruno
中科院分区：
文献类型：
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作者：
Barreto Bezerra, Jose Clecildo;Arantes, Morgana Elias;Neves Junior, Bruno
血吸虫病是由血吸虫属寄生虫引起的一种被忽视的热带疾病。在巴西，只有曼氏血吸虫会引起这种疾病。世界卫生组织估计，2012年全世界约有2.49亿人面临感染这种疾病的风险。控制该病的主要策略是对生活在流行地区的个人进行吡喹酮治疗。吡喹酮被大量用于治疗血吸虫病，目前有耐药性病例报告，表明需要发现新的药物。计算机药物重新定位是寻找抗血吸虫药物的一种节省时间和成本的策略。这项工作使用生物信息学工具来鉴定潜在的杀血吸虫药物。编制了S. mansoni潜在靶点列表，这些靶点是数据库“CDR”中基本过程的一部分，并且从科学文献中获得了作为被皮一部分的靶点。含有S. mansoni靶点的文件包含1,376个靶点，其中与399种药物相关的61个靶点与药物靶点具有同源性。在去除重复药物、先前研究中发现的药物以及结合位点保守性分析后，与102种药物相关的28个S. mansoni靶点只有60%或以上的活性位点保守。一些药物具有活性，值得验证这项研究，比如蒿甲醚。lumefantrine meloxicam。在发现的药物中，根据体内毒性低、非专利状态、logP等标准选择18种药物进行前瞻性实验分析
Schistosomiasis is a neglected tropical disease caused by parasites of the genus Schistosoma. In Brazil only Schistosoma mansoni causes this disease. The World Health Organization estimated in 2012 approximately 249 million people at risk of acquiring this disease around the world. The main strategy to control this disease is praziquantel treatment of individuals living in endemic areas. The drug praziquantel is used on a large scale in the treatment of schistosomiasis and currently there are reported cases of resistance, indicating the need to discover new drugs. In silico drug repositioning is a time and cost reducing strategy in the search for anti-Schistosoma agents. This work used bioinformatic tools to identify potential schistosomicidal drugs. A list was compiled of S. mansoni potential targets that are part of essential processes in the database "CDR and the targets that are part of the tegument were obtained in the scientific literature. The file with S. mansoni targets contained 1,376 targets, and of these only 61 targets associated with 399 drugs had homology with drug targets. After removal of duplicate drugs, drugs found in previous studies and after the analysis of the conservation of the binding site, only 28 S. mansoni targets associated with 102 drugs had 60% or more of the active site conserved. Some of the drugs had activity and are interesting to validate this study such as: artemether. lumefantrine, meloxicam. Among the drugs found 18 drugs were selected to be tested in prospective experimental assays according to the following criteria: low toxicity in vivo, off-patent status, and logP