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基于基因组的人类病原体药物靶点鉴定

Genome-Based Drug Target Identification in Human Pathogen .

作者信息

Qureshi Nosheen Afzal, Bakhtiar Syeda Marriam, Faheem Muhammad, Shah Mohibullah, Bari Ahmed, Mahmood Hafiz M, Sohaib Muhammad, Mothana Ramzi A, Ullah Riaz, Jamal Syed Babar

机构信息

Department of Bioinformatics and Biosciences, Capital University of Science and Technology, Islamabad, Pakistan.

Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan.

出版信息

Front Genet. 2021 Mar 25;12:564056. doi: 10.3389/fgene.2021.564056. eCollection 2021.

Abstract

() is an opportunistic Gram-positive, non-motile bacterium, which causes infective endocarditis, an inflammation of the inner lining of the heart. As has acquired resistance with the available antibiotics, therefore, there is a dire need to find new therapeutic targets and potent drugs to prevent and treat this disease. In the current study, an approach is utilized to link genomic data of species with its proteome to identify putative therapeutic targets. A total of 1,138 core proteins have been identified using pan genomic approach. Further, using subtractive proteomic analysis, a set of 18 proteins, essential for bacteria and non-homologous to host (human), is identified. Out of these 18 proteins, 12 cytoplasmic proteins were selected as potential drug targets. These selected proteins were subjected to molecular docking against drug-like compounds retrieved from ZINC database. Furthermore, the top docked compounds with lower binding energy were identified. In this work, we have identified novel drug and vaccine targets against , of which some have already been reported and validated in other species. Owing to the experimental validation, we believe our methodology and result are significant contribution for drug/vaccine target identification against -caused infective endocarditis.

摘要

(某菌)是一种机会性革兰氏阳性、无运动性的细菌,可引起感染性心内膜炎,即心脏内膜的炎症。由于该菌已对现有抗生素产生耐药性,因此迫切需要寻找新的治疗靶点和有效药物来预防和治疗这种疾病。在当前研究中,采用了一种方法将该菌的基因组数据与其蛋白质组联系起来,以识别潜在的治疗靶点。使用泛基因组方法共鉴定出1138个核心蛋白。此外,通过减法蛋白质组分析,鉴定出一组对细菌至关重要且与宿主(人类)无同源性的18种蛋白质。在这18种蛋白质中,选择了12种细胞质蛋白作为潜在的药物靶点。这些选定的蛋白质与从ZINC数据库检索到的类药物化合物进行分子对接。此外,还鉴定出对接能量较低的顶级化合物。在这项工作中,我们已经鉴定出针对该菌的新型药物和疫苗靶点,其中一些已在其他物种中报道并得到验证。由于实验验证,我们相信我们的方法和结果对针对该菌引起的感染性心内膜炎的药物/疫苗靶点鉴定具有重要贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3458/8027347/f841d37ec531/fgene-12-564056-g001.jpg

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