Bioinformatics Research Group, Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Indonesia, Kampus UI, Depok, 16424, Indonesia.
BMC Bioinformatics. 2018 Nov 20;19(Suppl 14):419. doi: 10.1186/s12859-018-2387-8.
Ebola still remains as one of the most problematic infectious diseases in Africa with a high rate of mortality. Although this disease has been known for an almost half-century, there are no vaccines and drugs available in the market to treat Ebola. Zaire ebolavirus (EBOV), a single-stranded RNA virus which belongs to Filoviridae family and Mononegavirales order, is one of the virus causing Ebola. As one of seven proteins that EBOV encodes, Ebola virus nucleoprotein (EBOV NP) plays an imperative role in EBOV proliferation cycle. Therefore, the development of a new Ebola treatment can be targeted towards EBOV NP.
In this work, we screened about 190,084 natural product compounds from ZINC15 database through in silico virtual screening and flexible docking simulation. Furthermore, the bioavailability and toxicity prediction have been conducted as well. Two best ligands according to the simulation and prediction tests were progressed into the molecular dynamics simulation.
In the end, we found that our proposed ligands, namely α-lipomycin (ZINC56874155) and 3-(((S)-1-amino-1,2,3,4-tetrahydroisoquinolin-5-yl)methyl)-5-((5-((5R,7S)-5,7-dihydroxy-3-oxodecyl)-2-hydroxyphenoxy) methyl)pyrrolo[3,4-b]pyrrol-5-ium (ZINC85628951), showed the promising results to be developed as a lead compounds for treating Ebola. Therefore, an experimental study is required to validate their inhibition activities against EBOV NP.
埃博拉仍然是非洲最具问题的传染病之一，死亡率很高。尽管这种疾病已经存在了近半个世纪，但目前市场上还没有治疗埃博拉的疫苗和药物。扎伊尔埃博拉病毒（EBOV）是一种单链 RNA 病毒，属于丝状病毒科和单负链病毒目，是引起埃博拉的病毒之一。作为 EBOV 编码的七种蛋白之一，埃博拉病毒核蛋白（EBOV NP）在 EBOV 增殖周期中起着至关重要的作用。因此，开发新的埃博拉治疗方法可以针对 EBOV NP。
在这项工作中，我们通过计算机虚拟筛选和柔性对接模拟筛选了来自 ZINC15 数据库的大约 190,084 种天然产物化合物。此外，还进行了生物利用度和毒性预测。根据模拟和预测测试，选择了两种最佳配体进行分子动力学模拟。
最后，我们发现我们提出的两种配体，即α-脂霉素（ZINC56874155）和 3-(((S)-1-氨基-1,2,3,4-四氢异喹啉-5-基)甲基)-5-((5-((5R,7S)-5,7-二羟基-3-氧代癸基)-2-羟基苯氧基)甲基)吡咯并[3,4-b]吡咯-5-鎓（ZINC85628951），显示出作为治疗埃博拉的先导化合物的有前途的结果。因此，需要进行实验研究来验证它们对 EBOV NP 的抑制活性。
