Indolylurea SST21 Targets Turnip Mosaic Virus Coat Protein to Disrupt Virion Assembly and Activate Host Defense

The turnip mosaic virus (TuMV) is an RNA virus that poses a significant threat to crops. The coat protein (CP) plays a crucial role in the viral life cycle, including mediating host infection and cell-to-cell movement, which makes it an ideal target for antiviral drug development. In this study, a series of structurally diverse synthetic indolylureas were screened against TuMV CP using high-throughput methods such as isothermal titration calorimetry (ITC) and microscale thermophoresis (MST). This led to the identification of compound SST21, which exhibits a high affinity for TuMV CP. Further experiments revealed that SST21 also binds to other homologous coat proteins from the Potyvirus genus, suggesting its potential as a broad-spectrum antiviral agent. Through molecular docking and point-mutation validation, the H183A residue in TuMV CP was identified as a key site for SST21 binding. In vivo experiments demonstrated that SST21 exhibits superior antiviral activity compared with ningnanmycin. Transmission electron microscopy observations indicated that SST21 disrupts the viral particle integrity. Additionally, omics analysis and defense enzyme activity assays showed that this compound was also found to modulate the plant immune responses. Together, these findings provide new insights into and experimental evidence for the development of novel plant antiviral strategies.