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.