Targeting the Erv29 cargo receptor disrupts effector secretion and confers broad-spectrum resistance against fungal pathogens

Plant diseases pose threat to global agricultural productivity and food security. Targeting conserved pathogenicity mechanisms offers a sustainable strategy for antifungal development. In plant pathogenic fungi, effectors suppress host immunity to facilitate infection. Given the precise regulation of effector delivery, key components of this secretion pathway emerge as attractive targets for the antifungal agents. Previously, we identified the cargo receptor MoErv29 in Magnaporthe oryzae as a key regulator of effector secretion. Here, in this study, we define MoErv29 cargo recognition mechanism and reveals a critical binding pocket essential for the pathogenicity of M. oryzae . Based on the predicted structure, we discover a small-molecule compound 0442, which inhibits MoErv29 function and reduces the severity of rice blast. The evolutionary conservation of this pocket allowed 0442 to exhibit broad-spectrum activity against a wide range of plant fungal pathogens. Together, these findings establish Erv29 as a validated molecular target and provide a framework for the development of a new class of broad-spectrum antifungal agents.