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用于鉴定……中新型治疗药物靶点的消减基因组学方法

Subtractive Genomics Approach for Identification of Novel Therapeutic Drug Targets in .

作者信息

Fatoba Abiodun Joseph, Okpeku Moses, Adeleke Matthew Adekunle

机构信息

Discipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Westville, P/Bag X54001, Durban 4000, South Africa.

出版信息

Pathogens. 2021 Jul 21;10(8):921. doi: 10.3390/pathogens10080921.

Abstract

infection is a sexually transmitted infection that causes urethritis, cervicitis, and pelvic inflammatory disease (PID) in men and women. The global rise in antimicrobial resistance against recommended antibiotics for the treatment of infection has triggered the need to explore novel drug targets against this pathogen. The application of a bioinformatics approach through subtractive genomics has proven highly instrumental in predicting novel therapeutic targets against a pathogen. This study aimed to identify essential and non-homologous proteins with unique metabolic pathways in the pathogen that could serve as novel drug targets. Based on this, a manual comparison of the metabolic pathways of and the human host was done, generating nine pathogen-specific metabolic pathways. Additionally, the analysis of the whole proteome of using different bioinformatics databases generated 21 essential, non-homologous, and cytoplasmic proteins involved in nine pathogen-specific metabolic pathways. The further screening of these 21 cytoplasmic proteins in the DrugBank database generated 13 druggable proteins, which showed similarity with FDA-approved and experimental small-molecule drugs. A total of seven proteins that are involved in seven different pathogen-specific metabolic pathways were finally selected as novel putative drug targets after further analysis. Therefore, these proposed drug targets could aid in the design of potent drugs that may inhibit the functionality of these pathogen-specific metabolic pathways and, as such, lead to the eradication of this pathogen.

摘要

[病原体名称]感染是一种性传播感染,可导致男性和女性的尿道炎、宫颈炎和盆腔炎(PID)。全球针对治疗[病原体名称]感染的推荐抗生素的抗菌耐药性上升,引发了探索针对这种病原体的新型药物靶点的需求。通过消减基因组学应用生物信息学方法已被证明在预测针对病原体的新型治疗靶点方面非常有用。本研究旨在鉴定该病原体中具有独特代谢途径的必需且非同源的蛋白质,这些蛋白质可作为新型药物靶点。基于此,对[病原体名称]和人类宿主的代谢途径进行了人工比较,产生了九条病原体特异性代谢途径。此外,使用不同的生物信息学数据库对[病原体名称]的全蛋白质组进行分析,产生了参与九条病原体特异性代谢途径的21种必需、非同源和细胞质蛋白质。在DrugBank数据库中对这21种细胞质蛋白质进行进一步筛选,产生了13种可成药蛋白质,这些蛋白质与FDA批准的和实验性小分子药物具有相似性。经过进一步分析,最终选择了参与七种不同病原体特异性代谢途径的七种蛋白质作为新型推定药物靶点。因此,这些提出的药物靶点有助于设计可能抑制这些病原体特异性代谢途径功能的强效药物,从而导致根除这种病原体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/190d/8402164/3f6f9e532a69/pathogens-10-00921-g001.jpg

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