Hu Fan, Lei Rong, Deng Yu-Fang, Wang Jun, Li Gui-Fen, Wang Chao-Nan, Li Zhi-Hong, Zhu Shui-Fang
College of Plant Protection, China Agricultural University Beijing 100193 China
Institute of Plant Quarantine, Chinese Academy of Inspection and Quarantine Beijing 100029 China.
RSC Adv. 2018 Mar 16;8(19):10532-10540. doi: 10.1039/c8ra01311j. eCollection 2018 Mar 13.
To control plant viruses, viral RNA silencing suppressors are important drug targets due to their key roles in interfering antiviral RNA silencing. Here we have presented a strategy, combining virtual and experimental screening, to discover the inhibitors of viral suppressor. By docking 157 026 compounds from a natural product library into P19 model, eighteen candidate compounds were selected. Candidates VS2, VS12, VS14 and VS15 displayed strong binding ability to P19 in the surface plasmon resonance imaging assay with values of 136.2, 111.6, 81.2 and 124.5 nM, respectively. Then the inhibition activities of these inhibitors on the association between P19 and siRNA were also affirmed by electrophoretic mobility shift assay. Moreover, the antiviral effects on plants showed that compounds VS14 and VS15 both exhibited antiviral activities against Tomato bushy stunt virus (TBSV) with inhibition rates of 32.35% and 16.61% in 11 dpi, respectively. This strategy would be a powerful tool for the discovery of novel antiviral agents and provide new insights into the control of plant viruses.
为了控制植物病毒，病毒RNA沉默抑制因子因其在干扰抗病毒RNA沉默中的关键作用而成为重要的药物靶点。在此，我们提出了一种结合虚拟筛选和实验筛选的策略，以发现病毒抑制因子的抑制剂。通过将天然产物库中的157026种化合物对接至P19模型，筛选出了18种候选化合物。在表面等离子体共振成像分析中，候选化合物VS2、VS12、VS14和VS15对P19表现出较强的结合能力，其解离常数分别为136.2、111.6、81.2和124.5 nM。然后，通过电泳迁移率变动分析也证实了这些抑制剂对P19与小干扰RNA（siRNA）结合的抑制活性。此外，对植物的抗病毒效果表明，化合物VS14和VS15对番茄丛矮病毒（TBSV）均表现出抗病毒活性，在接种后11天的抑制率分别为32.35%和16.61%。该策略将成为发现新型抗病毒剂的有力工具，并为植物病毒的防治提供新的思路。
