Sarukhanyan Edita, Shityakov Sergey, Dandekar Thomas
Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Department of Anesthesia and Critical Care, University Hospital Würzburg, Oberdürrbacher Str. 6, 97080 Würzburg, Germany.
ACS Omega. 2018 May 31;3(5):5281-5290. doi: 10.1021/acsomega.8b00223. Epub 2018 May 16.
After a large outbreak in Brazil, novel drugs against Zika virus became extremely necessary. Evaluation of virus-based pharmacological strategies concerning essential host factors brought us to the idea that targeting the Axl receptor by blocking its dimerization function could be critical for virus entry. Starting from experimentally validated compounds, such as RU-301, RU-302, warfarin, and R428, we identified a novel compound 2' (R428 derivative) to be the most potent for this task amongst a number of alternative compounds and leads. The improved affinity of compound 2' was confirmed by molecular docking as well as molecular dynamics simulation techniques using implicit solvation models. The current study summarizes a new possibility for inhibition of the Axl function as a potential target for future antiviral therapies.
在巴西爆发大规模疫情后，对抗寨卡病毒的新型药物变得极为必要。对针对关键宿主因子的基于病毒的药理学策略进行评估后，我们想到通过阻断Axl受体的二聚化功能来靶向该受体可能对病毒进入至关重要。从经过实验验证的化合物，如RU - 301、RU - 302、华法林和R428出发，我们在众多替代化合物和先导化合物中确定了一种新型化合物2'（R428衍生物）是执行此任务最有效的。使用隐式溶剂化模型的分子对接以及分子动力学模拟技术证实了化合物2'具有更高的亲和力。本研究总结了抑制Axl功能作为未来抗病毒治疗潜在靶点的一种新可能性。
