Discovery of novel inhibitors of RNA silencing suppressor P19 based on virtual screening
作者： Fan Hu , Rong Lei , Yu-Fang Deng , Jun Wang , Gui-Fen Li
DOI: 10.1039/C8RA01311J
关键词: Docking (molecular) 、 RNA silencing 、 Tomato bushy stunt virus 、 Virtual screening 、 Biochemistry 、 Chemistry 、 Electrophoretic mobility shift assay 、 Plant virus 、 In vivo 、 Gene silencing
摘要: To control plant viruses, viral RNA silencing suppressors are important drug targets due to their key roles in interfering antiviral silencing. Here we have presented a strategy, combining virtual and experimental screening, discover the inhibitors of suppressor. By docking 157 026 compounds from natural product library into P19 model, eighteen candidate were selected. Candidates VS2, VS12, VS14 VS15 displayed strong binding ability surface plasmon resonance imaging assay with KD values 136.2, 111.6, 81.2 124.5 nM, respectively. Then inhibition activities these on association between siRNA also affirmed by electrophoretic mobility shift assay. Moreover, effects plants showed that both exhibited against Tomato bushy stunt virus (TBSV) vivo rates 32.35% 16.61% 11 dpi, This strategy would be powerful tool for discovery novel agents provide new insights viruses.
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