Targeting ferroptosis in Pyricularia Oryzae to suppress rice blast (INFIRE)

Rice blast fungus (Pyricularia oryzae) destroys enough rice annually to feed 60 million people, representing a critical threat to global food security as 551 million tons of milled rice will be needed by 2030. The pathogen undergoes iron-dependent cell death (ferroptosis) during infection, which paradoxically enhances its virulence, making this process a novel and unexplored therapeutic target. INFIRE aims to develop new antifungal compounds that disrupt ferroptosis through three complementary approaches: suppressing lipid peroxidation using natural and synthetic antioxidants, modulating iron availability with chelators, and inhibiting iron-dependent NOX enzymes involved in the ferroptosis pathway. The project will initially screen natural compounds, then synthesize optimized analogs and design hybrid molecules that combine multiple mechanisms of action. The expected outcome is identification of new chemical classes for rice blast management, advancing both fundamental understanding of fungal ferroptosis and practical agrochemical applications. This represents a paradigm shift from traditional fungicides toward targeting the pathogen's own regulated cell death mechanisms, offering potential for more effective and sustainable disease control strategies.