Beyond Fungitoxicity: Recent Achievements in Targeted Fungicide Discovery

Phytopathogenic fungi pose a constant threat to worldwide agricultural production. Given the widespread development of fungicide resistance and increasing environmental and regulatory constraints, precision disease-control strategies are urgently needed to enhance selectivity, durability, and sustainability. This review critically examines recent advances in targeted fungicide discovery against phytopathogenic fungi. We categorize these strategies into three complementary groups: (1) targeting fungal biological processes that are essential or infection-associated; (2) disarming pathogen virulence by interfering with immune evasion and effector-mediated interactions; and (3) activating or redirecting host defence through host-directed or dual-action interventions. We compare these strategies with respect to mechanistic rationale, expected selectivity, resistance risk, and field-deployment challenges. Additionally, we discuss emerging enabling technologies—including compound repurposing, structural biology, and artificial intelligence-assisted fungicide design—that accelerate target identification and lead optimization. These strategies have begun to facilitate the discovery of compounds with improved specificity and disease-control potential. We believe that the integrated application of these approaches may support the development of more selective and potentially durable disease-control agents.