Fabrication of novel purine nucleoside derivatives bearing a cinnamic acid moiety for controlling plant viral diseases: synthesis, anti-tobacco mosaic virus activity, and mechanistic study

Abstract

BACKGROUND

In recent years, many plant viral diseases have triggered global epidemics, posing an intractable threat to food safety and the global economy. However, antiviral agents currently remain insufficient due to their limited control effect and photothermal instability. Consequently, the development of antiviral alternatives with high efficiency and eco-friendly manifestation is a matter of great urgency and importance.

RESULTS

Herein, 34 purine nucleoside derivatives bearing a cinnamic acid building block were constructed and underwent evaluation of anti-tobacco mosaic virus (anti-TMV) potency. Biological assays demonstrated that compound A₁₄ displayed excellent curative activity with a half maximal effective concentration (EC₅₀) of 274.25 mg L⁻¹, which surpassed that of reference agents ribavirin (783.54 mg L⁻¹) and ningnanmycin (283.26 mg L⁻¹). The mechanism of action was further investigated through fluorescence confocal microscopy, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), TMV self-assembly, molecular docking, fluorescence titration, and transmission electron microscopy. Outcomes indicated that A₁₄ could prevent the systemic transmission and biosynthesis of TMV in plants, in addition to blocking the self-assembly of TMV via interacting with TMV-coat protein.

CONCLUSION

Our research efforts resulted in the verification of compound A₁₄ as novel antiviral agent alternative, which possessed the dual function of inhibiting the biosynthesis and self-assembly process of TMV, for effective controlling plant viral diseases. © 2025 Society of Chemical Industry.