Chowdhury Umar Faruq, Saba Abdullah Al, Sufi Abu Sufian, Khan Akib Mahmud, Sharmin Ishrat, Sultana Aziza, Islam Md Ohedul
Sarkari Karmachari Hospital, Fulbaria, Dhaka, Bangladesh.
Biochemistry and Molecular Biology, University of Dhaka, Bangladesh.
Heliyon. 2021 Jun 16;7(6):e07320. doi: 10.1016/j.heliyon.2021.e07320. eCollection 2021 Jun.
is an emerging pathogen that has been implicated in numerous unpropitious pregnancy events in humans and ruminants. Taking into account its association with abortigenic events, possible modes of transmission, and future risk, immediate clinical measures are required to prevent widespread damage caused by this organism and hence this study. Here, a subtractive proteomics approach was employed to identify druggable proteins of . Considering the essential genes, antibiotic resistance proteins, and virulence factors, 676 unique important proteins were initially identified for this bacterium. Afterward, NCBI BLASTp performed against human proteome identified 223 proteins that were further pushed into KEGG Automatic Annotation Server (KAAS) for automatic annotation. Using the information from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database 14 specific metabolic pathways were identified with respect to humans. Analyzing the data from KAAS and KEGG databases, forty-eight metabolic pathway-dependent, and seventy metabolic pathway independent proteins were identified. Standalone BLAST search against DrugBank FDA approved drug targets revealed eight proteins that are finally considered druggable proteins. Prediction of three-dimensional structures was done for the eight proteins through homology modeling and the Ramachandran plot model showed six models as a valid prediction. Finally, virtual screening against MurB protein was performed using FDA approved drugs to employ the drug repositioning strategy. Three drugs showed promising docking results that can be used for therapeutic purposes against following the clinical validation of the study.
是一种新兴病原体,与人类和反刍动物的众多不良妊娠事件有关。考虑到其与致流产事件的关联、可能的传播方式以及未来风险,需要立即采取临床措施来预防这种生物体造成的广泛损害,因此开展了本研究。在此,采用减法蛋白质组学方法来鉴定[病原体名称]的可成药蛋白。考虑到必需基因、抗生素抗性蛋白和毒力因子,最初为这种细菌鉴定出676种独特的重要蛋白。随后,针对人类蛋白质组进行的NCBI BLASTp分析鉴定出223种蛋白,这些蛋白被进一步推送至KEGG自动注释服务器(KAAS)进行自动注释。利用京都基因与基因组百科全书(KEGG)数据库中的信息,确定了14条与人类相关的特定代谢途径。分析来自KAAS和KEGG数据库的数据,鉴定出48种依赖代谢途径的蛋白和70种不依赖代谢途径的蛋白。针对DrugBank中FDA批准的药物靶点进行的独立BLAST搜索揭示了8种最终被认为是可成药的蛋白。通过同源建模对这8种蛋白进行了三维结构预测,拉氏图模型显示有6个模型预测有效。最后,使用FDA批准的药物对MurB蛋白进行虚拟筛选,以采用药物重新定位策略。三种药物显示出有前景的对接结果,在本研究经过临床验证后,可用于针对[病原体名称]的治疗目的。