Novel cinnamic acid-ribavirin conjugates: design, synthesis, antiviral activity against tobacco mosaic virus and mechanistic study.

BACKGROUND: Plant viral diseases represent a serious threat to global agricultural productivity and sustainable development. Most commercially available antiviral agents function primarily as protectants. However, the long-term and repetitive application of conventional broad-spectrum antiviral agents has led to the emergence of resistance, diminishing their field efficacy. To discover new antiviral drugs, we designed and synthesized 31 novel ribavirin derivatives incorporating cinnamic acid motifs via a lead optimization strategy and evaluated their anti-tobacco mosaic virus (TMV) activity.

RESULTS: Biological assays revealed that compound A23 exhibited potent protective activity against TMV, with an EC₅₀ of 131.1 μg/mL, which was significantly lower than that of ribavirin (529.9 μg/mL) and ningnanmycin (248.4 μg/mL). Further research indicated that compound A23 significantly enhanced the activity of defense-related enzymes and regulated the plant hormone signal transduction pathway as well as the plant-pathogen interaction pathway in tobacco plants. Notably, it upregulated the expression of key genes NPR1 and PR-1 in the salicylic acid (SA) signaling pathway, thereby effectively enhancing the plant's defense response and resistance against TMV.

CONCLUSION: These results demonstrate that compound A23 possesses remarkable bioactivity and effectively controls TMV infection by inducing host plant immunity. Its promising efficacy supports its potential as a candidate agent for controlling plant viral diseases and warrants further investigation. © 2025 Society of Chemical Industry.