A novel highly antifungal compound ZJS-178 targeting myosin I inhibits the endocytosis and mycotoxin biosynthesis of Fusarium graminearum

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.