In Silico Designed Axl Receptor Blocking Drug Candidates Against Zika Virus Infection

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.巴西暴发大规模寨卡病毒（Zika virus）疫情后，抗寨卡病毒新型药物的研发需求极为迫切。通过评估针对宿主关键因子的病毒靶向药理学策略，我们提出：通过阻断Axl受体（Axl receptor）的二聚化功能来靶向该受体，可能是调控病毒入侵的关键靶点。本研究从经实验验证的化合物（如RU-301、RU-302、华法林及R428）出发，在诸多备选化合物与先导化合物中，筛选出新型化合物2′（R428衍生物）为该研究场景下活性最强的候选化合物。化合物2′的亲和力提升效果，通过分子对接（molecular docking）及采用隐式溶剂化模型（implicit solvation models）的分子动力学模拟（molecular dynamics simulation）技术得到了验证。本研究为以抑制Axl功能为靶点的新型抗病毒治疗策略提供了全新的潜在方向。