a Department of Chemical Pathology, Faculty of Health Sciences, University of Pretoria and National Health Laboratory Service Tshwane Academic Division , Pretoria , South Africa.
b School of Health Sciences, University of Kwazulu-Natal, Westville Campus , Durban , South Africa.
J Biomol Struct Dyn. 2019 Sep;37(15):4104-4119. doi: 10.1080/07391102.2018.1544509. Epub 2018 Dec 24.
Ebola is a dangerous virus transmitted by animals and humans and to date there is no curable agent for such a deadly infectious disease. In this study, pharmacoinformatics-based methods were adopted to find effective novel chemical entities against Ebola virus. A well predictive and statistical robust pharmacophore model was developed from known Ebola virus inhibitors collected from the literature. The model explained the significance of each of hydrogen bond acceptor and donor, and two hydrophobic regions for activity. The National Cancer Institute and Asinex (Antiviral library) databases were screened using the final validated pharmacophore model. Initial hits were further screened with a set of criteria and finally eight molecules from both databases were proposed as promising anti Ebola agents. Further molecular docking and molecular dynamics studies were carried out and it was found that the proposed molecules possessed capability to interact with amino residues of Ebola protein as well as retaining equilibrium of protein-ligand systems. Finally, the binding energies were calculated using molecular mechanics Poisson-Boltzmann surface area approach and all proposed molecules showed strong binding affinity towards the Ebola protein receptor. Communicated by Ramaswamy H. Sarma.
埃博拉是一种由动物和人类传播的危险病毒，迄今为止，对于这种致命的传染病还没有可治愈的药物。在这项研究中，采用基于药物信息学的方法来寻找针对埃博拉病毒的有效新型化学实体。从文献中收集的已知埃博拉病毒抑制剂中开发了一个具有良好预测性和统计稳健性的药效团模型。该模型解释了每个氢键受体和供体以及两个疏水区对活性的重要性。使用最终验证的药效团模型对国家癌症研究所和 Asinex（抗病毒文库）数据库进行了筛选。初始命中物进一步通过一系列标准进行筛选，最终从两个数据库中提出了 8 种分子作为有前途的抗埃博拉药物。进一步进行了分子对接和分子动力学研究，发现所提出的分子具有与埃博拉蛋白的氨基酸残基相互作用的能力，并且保持了蛋白-配体系统的平衡。最后，使用分子力学泊松-玻尔兹曼表面积方法计算了结合能，所有提出的分子都表现出对埃博拉蛋白受体的强结合亲和力。Ramaswamy H. Sarma 通讯。
