Design and Synthesis of a Novel Guanidino-Modified Nucleoside and Its Antiviral Activity against Potato Virus Y.

Potato virus Y (PVY) causes significant damage to crops worldwide. Nucleoside analogs and their derivative drugs are currently a research hot spot in antiviral medications. We designed and synthesized a nucleoside guanidine compound FluoroGuanidoNucleosin (FGN) with anti-plant virus effects by structural modification of the nucleoside scaffold. The structure of compound FGN was characterized by 1H NMR, 13C NMR, and HRMS, and is named (R)-N-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-group)-2-oxo-1,2-dihydropyrimidine-4-group)-3-guanidine-4-(2,4,5-trifluorophenyl)butanamide, and the molecular formula of compound FGN is C20H23N6O6F3. FGN achieved high antiviral activities against PVY in Nicotiana tabacum, with inactivation (82.13%), curative (72.69%), and protective (68.75%) activity at 500 μg/mL. Furthermore, RNA-seq revealed FGN-induced DEGs enriched in KEGG pathways such as plant-pathogen interaction, plant hormone signal transduction, and ribosome. In addition, molecular docking indicated that FGN potentially binds to PVY NIb and PVY NIa-Pro. The design and synthesis of the nucleoside guanidine compound FGN provides a theoretical basis for the development and application of antiviral drugs.