Discovery of Novel Coumarin Derivatives as Potential Eco-Friendly Antivirals against Cucumber Mosaic Virus

Coumarins are widely distributed natural products with diverse biological activities. In this study, 54 novel coumarin derivatives bearing benzyl chloride and dithioacetal moieties were designed, synthesized, and evaluated for antiviral activity against cucumber mosaic virus (CMV). Several compounds exhibited superior efficacy compared to the commercial agent ningnanmycin. Notably, compound E27 showed the strongest in vivo protective activity, outperforming both ningnanmycin and chitosan oligosaccharide (COS). Mechanistic studies revealed that E27 enhanced defense-related enzyme activities, increased chlorophyll accumulation, and mitigated CMV-induced photosynthetic damage. Transcriptomic analysis demonstrated that E27 significantly upregulated photosynthesis-related pathways, with chlorophyll a/b-binding protein (CAB) identified as a key responsive gene. Functional assays confirmed that CAB silencing reduced host resistance, whereas CAB overexpression suppressed CMV proliferation. In addition, in silico ADME analysis indicated favorable pharmacokinetic properties and low ecological risk. These results highlight E27 as a promising lead for eco-friendly antiviral agrochemical development.