Eco-Friendly Cinnamic Acid Derivatives Containing Glycoside Scaffolds as Potential Antiviral Agents

Natural products are a crucial source in the development of new eco-friendly antiviral agents to control plant viral diseases. In our previous studies, some ferulic acid derivatives with good antiviral activity were obtained as an immune activator. To continue the discovery of eco-friendly antiviral agents, different monosaccharides were introduced into cinnamic acid skeletons by an activity-based strategy to obtain a series of cinnamic acid derivatives containing glycoside scaffolds, and their antiviral activities against tobacco mosaic virus (TMV) and tomato spotted wilt virus (TSWV) were evaluated. Among them, compound 8d showed the greatest protective activities against TMV and TSWV, with the EC₅₀ values of 128.5 and 236.8 μg mL^-1, respectively, which were superior to those of ningnanmycin (238.5 and 315.7 μg mL^-1, respectively). Moreover, compound 8d could significantly improve the defense enzyme activities of peroxidase, chitinase, and β-1,3-glucanase. Proteomic and transcriptome analyses indicated that compound 8d regulated gene transcription and protein expression levels involved in the defense response to resist virus infection. The present study revealed that compound 8d is a potential lead candidate for the development of novel, eco-friendly, and natural-product-based antiviral agents.