Novel cinnamic acid derivatives enable the induction of chloroplast‐associated immunity and interaction with viral coat proteins for plant viral disease control

Abstract BACKGROUND Viral diseases remain persistent global challenges to public health systems and agricultural productivity, while current antiviral strategies are constrained by their narrow therapeutic spectrum and overreliance on unimodal mechanisms. These critical limitations highlight the imperative to develop new antiviral agents with innovative chemical scaffolds and multimodal mechanisms of action. RESULTS In this study, 31 novel cinnamic acid derivatives were synthesized and their inhibitory activities against tobacco mosaic virus (TMV) in tobacco hosts were evaluated. Compound B 7 , which features a p ‐bromophenyl group connected via a piperidine linker and a sulfonamide pharmacophore, demonstrated the most potent antiviral efficacy, with half maximal effective concentration (EC 50 ) values of 224.75 mg L −1 (protective) and 332.59 mg L −1 (curative), outperforming the positive control ningnanmycin (245.67 and 340.52 mg L −1 , respectively). Mechanistic investigations revealed that B 7 significantly reduced viral accumulation in chloroplast‐associated regions, thereby enhancing plant vitality and promoting chloroplast‐mediated immune regulation. Meanwhile, B 7 can also increase the salicylic acid content in plants. These effects ultimately lead to activated plant resistance. Furthermore, B 7 also exhibited strong binding affinity ( K a = 1.19 × 10 5 m −1 ) to TMV coat protein (TMV‐CP), directly disrupting viral structural integrity and inhibiting replication. CONCLUSION This study identifies B 7 as the optimal antiviral agent with superior efficacy and biosafety, defines critical structure–activity relationship principles governing cinnamic acid‐based antiviral agent design, and mechanistically validates its dual‐action mechanisms involving chloroplast‐potentiated systemic immunity and direct TMV‐CP interactions. It provides an important reference for the development of efficient and multitarget antiviral agents. © 2026 Society of Chemical Industry.