Department of Biotechnology, Wolkite University, Wolkite, Ethiopia.
Department of Applied Biology, Adama Science and Technology University, Adama, Ethiopia.
Biomed Res Int. 2024 Jan 20;2024:5917667. doi: 10.1155/2024/5917667. eCollection 2024.
is an important pathogen worldwide that causes pneumococcal infections which are related to high rates of morbidity and mortality especially in young children, older adults, and immune-compromised persons. Antibiotic resistance in is a serious problem across the world from time to time, resulting in treatment failure and diminished value of older medicines. Therefore, the objective of this study was to identify new putative drug targets against serotype 23F by using subtractive genomics. By using bioinformatics tools such as NCBI, UniProt KB, PDB, KEGG, DEG, PSORTb, CD hit, DrugBank database, and other softwares, proteins involved in unique metabolic pathways of serotype 23F were studied. The result indicates that this serotype consists of 97 metabolic pathways of which 74 are common with that of human, and 23 pathways are unique to the serotype 23F. After investigation and analysis of essentiality, nonhomology, subcellular localization, having drug targets, and enzymatic activity, four proteins were prioritized as druggable targets. These druggable proteins include UDP-N-acetylglucosamine 1-carboxyvinyltransferase, UDP-N-acetyl muramate dehydrogenase, D-alanine-D-alanine ligase, and alanine racemase that are found in . serotype 23F. All these four proteins are essential, are nonhomologous with human proteins, have drug targets, and are located in cell cytoplasm. Therefore, the authors recommend these proteins to be used for efficient drug design against . serotype 23F after experimental validation for essentiality and druggability.
是一种重要的病原体,在全球范围内引起肺炎球菌感染,尤其是在儿童、老年人和免疫功能低下者中,与高发病率和死亡率有关。肺炎球菌对抗生素的耐药性是一个全球性的严重问题,导致治疗失败和旧药物价值降低。因此,本研究的目的是通过消减基因组学来确定针对 23F 血清型的新潜在药物靶标。通过使用生物信息学工具,如 NCBI、UniProtKB、PDB、KEGG、DEG、PSORTb、CD hit、DrugBank 数据库和其他软件,研究了涉及 23F 血清型独特代谢途径的蛋白质。结果表明,该血清型由 97 种代谢途径组成,其中 74 种与人类共有,23 种途径是 23F 血清型所特有的。在对必需性、非同源性、亚细胞定位、具有药物靶点和酶活性进行调查和分析后,优先选择了 4 种蛋白质作为可成药靶标。这些可成药的蛋白质包括 UDP-N-乙酰葡萄糖胺 1-羧基乙烯基转移酶、UDP-N-乙酰胞壁酸脱氢酶、D-丙氨酸-D-丙氨酸连接酶和丙氨酸消旋酶,它们存在于 23F 血清型中。所有这四种蛋白质都是必需的,与人类蛋白质没有同源性,具有药物靶点,并且位于细胞质中。因此,作者建议在实验验证必需性和成药性后,将这些蛋白质用于针对 23F 血清型的有效药物设计。