Isolation, Anti-TMV Activity, and Modes of Action of Novel Isochromene and Isoquinoline Derivatives from Streptomyces mirabilis YMZU50

Fourteen compounds, including three new isochromenes (1–3) and four new isoquinolines (4–7), were isolated from Streptomyces mirabilis YMZU50. The anti-tobacco mosaic virus (TMV) activities of compounds 1–8 and 13 were evaluated. Compound 6 exhibited the strongest inactivation and protective effects, with inhibition rates of 76.8 and 80.2%, respectively, surpassing the positive control ningnanmycin (45.8 and 43.6%). It also demonstrated curative effects in mildly (grades 1–3) and severely (grade 9) infected plants, reducing severity to grades 1 and 3, respectively. Transmission electron microscopy (TEM) observations confirmed a direct viral particle disruption. Physiological and biochemical analyses revealed a significant enhancement of defense-related enzymes and salicylic acid (SA)accumulation in tobacco. Transcriptomic profiling indicated strong upregulation of photosynthesis-related genes, while metabolomic analysis revealed changes in defense-associated metabolites. These results demonstrate compound 6 as a promising eco-friendly antiviral agent with multimodal TMV control mechanisms, underscoring the potential of Streptomyces-derived products for sustainable crop protection.