Tambunan Usman Sumo Friend, Alkaff Ahmad Husein, Nasution Mochammad Arfin Fardiansyah, Parikesit Arli Aditya, Kerami Djati
Bioinformatics Research Group, Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Indonesia, Depok 16424, Indonesia.
Bioinformatics Research Group, Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Indonesia, Depok 16424, Indonesia.
J Mol Graph Model. 2017 Jun;74:366-378. doi: 10.1016/j.jmgm.2017.04.001. Epub 2017 Apr 21.
Ebola Hemorrhagic Fever (EHF) is a disease caused by viruses from genus Ebolavirus. Zaire ebolavirus (EBOV) is the deadliest species which has 76% case fatality rate. Up until now, there is no U.S. Food and Drug Administration (FDA) approved drugs to treat EHF. Antiviral drug based on EBOV N-terminal heptad repeat glycoprotein-2 (NHR GP2) Ectodomain inhibitor is one kind of treatment that has not well developed. NHR GP2 Ectodomain has an important role in the process of EBOV entry into the cell through endocytosis mechanism. In this study, we used in silico methods to investigate the activity of commercial cyclic peptide conjugated to Human Immunodeficiency Virus type 1 Trans-activator of the transcription (HIV-1 Tat) peptide as ligands which act as an inhibitor of EBOV NHR GP2 Ectodomain. The commercial cyclic peptides which we used in this study were obtained from the selected chemical companies. Conjugation of the commercial cyclic peptides to HIV-1 Tat peptide was done in order to accumulate it inside the endosome. The ligands which had the best inhibition properties were screened using molecular docking and molecular dynamics simulation. Prediction of pharmacological properties of the peptides was done to choose the best drug candidate. The result of screening processes shows that Ligand 023 has the highest potency as the drug lead. The ligand needs to undergo further analysis through in vitro, in vivo, and a clinical trial to ensure that this ligand has a therapeutic ability as an antiviral drug for Ebola virus infection.
埃博拉出血热（EHF）是一种由埃博拉病毒属病毒引起的疾病。扎伊尔埃博拉病毒（EBOV）是最致命的毒株，病死率达76%。截至目前，美国食品药品监督管理局（FDA）尚未批准用于治疗EHF的药物。基于EBOV N端七肽重复糖蛋白-2（NHR GP2）胞外域抑制剂的抗病毒药物是一种尚未充分开发的治疗方法。NHR GP2胞外域在EBOV通过内吞作用机制进入细胞的过程中发挥重要作用。在本研究中，我们采用计算机模拟方法，研究与1型人类免疫缺陷病毒转录反式激活因子（HIV-1 Tat）肽偶联的商业环肽作为配体的活性，该配体可作为EBOV NHR GP2胞外域的抑制剂。我们在本研究中使用的商业环肽购自选定的化学公司。将商业环肽与HIV-1 Tat肽偶联，以便将其积聚在内体中。使用分子对接和分子动力学模拟筛选具有最佳抑制特性的配体。对肽的药理性质进行预测，以选择最佳候选药物。筛选过程结果表明，配体023作为药物先导物的效力最高。该配体需要通过体外、体内和临床试验进行进一步分析，以确保该配体具有作为埃博拉病毒感染抗病毒药物的治疗能力。
