Discovery of Arbutin as Novel Potential Antiviral Agent Against Tomato Yellow Leaf Curl Virus

Tomato yellow leaf curl virus (TYLCV), a major plant virus, infects multiple plant species, severely threatening global food security. Arbutin, a natural product used in cosmetics to reduce pigmentation, also exhibits antibacterial and anti-inflammatory properties. However, its potential in plant protection remains undocumented. This study reveals arbutin’s ability to inhibit TYLCV infection. In Nicotiana benthamiana, 100 μg/mL arbutin inhibited viral gene accumulation by up to 76.8%, surpassing ningnanmycin (65.8%) and ribavirin (39.5%). Besides, microscale thermophoresis indicated that arbutin bound strongly to the TYLCV coat protein (CP). Molecular docking indicated that arbutin interacted with ARG58, VAL65, and CYS69. RT-qPCR and Western blot experiments confirmed the crucial roles of these amino acids, especially VAL65, in viral infection. Transcriptome analysis revealed that mutating VAL65 affected plant–pathogen interaction pathways and MAPK signaling in host defense mechanisms. This study unveils arbutin’s novel antiviral function, providing crucial insights for developing new biopesticides against plant viruses.