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Updated: Mar 24, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Synthesis, antiviral activity and mechanistic insights into cytidine derivatives
Rui Wang1, Yueling Qin1, Ming Chen1
1State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals of Guizhou University, Guiyang, China.
Background:
Tobacco mosaic virus (TMV) is one of the most destructive plant pathogens. The modification of nucleosides is an effective method to develop anti-TMV agents. A series of novel cytidine derivatives were designed and synthesized, and their antiviral activities against TMV were evaluated systematically.
Results:
Activity assays revealed that 5z exhibited excellent protective and curative effects, with a half-effective concentration (EC50) of 191.84 μg mL-1, outperforming the control commercial agents ningnanmycin (240.79 μg mL-1) and ribavirin (622.22 μg mL-1). The mode of action (MoA) of 5z was thoroughly investigated through a multifaceted approach involving TMV-GFP agrobacterium infiltration inoculation, chlorophyll content measurement, defense enzyme activity analysis and molecular docking. Mechanistic studies revealed that 5z exerts its multi-target antiviral effects by specifically binding to the TMV coat protein (TMV-CP), while simultaneously triggering the plant's defense enzyme system and boosting photosynthetic efficiency.
Conclusion:
Structure-activity relationships (SARs) were established for the cytidine derivatives, providing guidance for the design of cytidine-based antiviral agents. Given its potent antiviral activity and unique mechanism of action, 5z shows strong promise as a novel antiviral agent. © 2026 Society of Chemical Industry.
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