Resveratrol Analog ResA1 Targeting MoYpk1 Exhibits Broad-Spectrum Antifungal Activity against Rice Blast

Rice blast, caused by Magnaporthe oryzae, is a devastating disease that severely threatens global rice production. The rapid emergence of fungicide resistance and environmental concerns necessitates new molecular targets and effective antifungal agents. Here, we identified MoYpk1, an AGC kinase, as a key regulator of M. oryzae pathogenesis and a novel fungicide target. Leveraging the 3D structure of MoYpk1-KD, we performed a structure-based virtual screening of a natural metabolite library and identified resveratrol as an antifungal inhibitor. Furthermore, we developed a resveratrol derivative, resveratrol analog 1 (ResA1), which exhibits significantly enhanced antifungal activity by specifically targeting E381, a previously unrecognized active site of MoYpk1. Importantly, ResA1 displays broad-spectrum antifungal activity against diverse plant pathogenic fungi while being safe for rice and humans. Our work not only elucidates the key role of MoYpk1 in M. oryzae virulence but also validates it as a promising target for the development of sustainable plant-protection strategies.