A novel highly antifungal compound ZJS-178 targeting myosin I inhibits the endocytosis and mycotoxin biosynthesis of Fusarium graminearum
Qiaowan Chen, Chang Liu, Hao Qi, Ningjie Wu, Zunyong Liu, Qin Tian, Xiaoxiao Zhu, Xiang‐dong Li, Yun Chen, Zhonghua Ma
Abstract
Chemical fungicides remain a primary tool for managing Fusarium head blight (FHB) due to the lack of resistant wheat cultivars. In this study, we synthesized 101 2-cyanoacrylate compounds and identified ZJS-178 as particularly effective against Fusarium graminearum (the causal agent of FHB), inhibiting both hyphal growth and conidial germination. Notably, ZJS-178 is specific to Fusarium species, with no impact on other fungi. It also shows no cross-resistance with other groups of fungicides, suggesting a unique mode of action. Mechanistic studies revealed that ZJS-178 targets myosin I in F. graminearum, inhibiting ATPase activity and disrupting endocytosis. Furthermore, ZJS-178 impairs toxisome formation, leading to reduced production of the mycotoxin deoxynivalenol (DON). These findings position ZJS-178 as a promising antifungal agent that could pave the way for developing a novel fungicide to manage FHB and other Fusarium-related diseases.