The present research was aiming to study In-Silico the effect of Glycyrrhizic Acid ammonium salt (GAS) and Salicylic acid (SA) on the coat protein of potato leafroll virus (PLRV). In addition, in-vitro studying the effect of (GAS NPs) and Salicylic acid (SA NPs) nanoparticles at concentrations 0.15, 0.30, 1.25 and 2.5 mM, respectively, to control, decline or reduce the presence of PLRV in potato plants Solanum tuberosum L. selena. (GAS NPs) and (SA NPs) were applied in the MS medium at concentrations 0.15, 0.30, 1.25 and 2.5 mM, respectively. Results revealed that, enhancement or decline the PLRV according to the initiation of specific pathways. The expression level of Kinase 3 gene increased significantly due to the two used concentrations of GAS NPs. While the expression of callose gene was upregulated significantly in response to treatment of PLRV infected plant with (GAS NPs) with concentration (0.30 mM). Treatment with (SA NPs) caused upregulation significance only of callose gene at (2.5 mM) concentration. The molecular modeling results of used compounds (glycyrrhizic acid ammonium salt and salicylic acid) showed highest score of binding and the best rms define value with a very good binding mode and perfect interactions with amino acids of the three subunits (A, B and C) forming the protein coat of leaf roll virus. Glycyrrhizic acid ammonium salt and salicylic acid nanoparticles could be perfect solution to produce potato plant free virus in-vitro. Further larger studies are needed to investigate the role of the studied compounds in vivo.