Labdane Diterpenoids with Anti-Tomato Spotted Wilt Virus Activity from Andrographis paniculata

In our ongoing research into Tomato spotted wilt virus (TSWV) inhibitors derived from natural products, a comprehensive phytochemical analysis of the whole plant of Andrographis paniculata was performed. This study afforded 29 labdane diterpenoids (1–29), including eight previously unreported compounds (1–8). Among these, compound 2 features an uncommon 6/6/5 tricyclic scaffold, while compound 5 possesses a distinct 6/6/6/5 tetracyclic framework. The structures of isolated compounds were unequivocally determined via NMR, HRESIMS, IR, UV, quantum chemical calculations, and X-ray crystallographic analysis. In anti-TSWV assays, compound 9 exhibited stronger protective activity (EC50: 100.7 μg/mL) than the positive control ningnanmycin (EC50: 107.5 μg/mL). Mechanistic studies, including RNA-sequencing analysis, revealed that compound 9 activates both the photosynthetic and salicylic acid pathways, enhances systemic acquired resistance, and thereby suppresses TSWV replication. This study offers valuable molecular leads and conceptual insights for the development of novel pesticides.