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

Fourteen compounds, including three new isochromenes (<b>1</b>-<b>3</b>) and four new isoquinolines (<b>4</b>-<b>7</b>), were isolated from <i>Streptomyces mirabilis</i> YMZU50. The anti-tobacco mosaic virus (TMV) activities of compounds <b>1</b>-<b>8</b> and <b>13</b> were evaluated. Compound <b>6</b> 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 <b>6</b> as a promising eco-friendly antiviral agent with multimodal TMV control mechanisms, underscoring the potential of <i>Streptomyces</i>-derived products for sustainable crop protection.