SP-141 targets Trs85 to inhibit rice blast fungus infection and functions as a potential broad-spectrum antifungal agent

Rice blast is a devastating disease worldwide, threatening rice production and food security. The blast fungus Magnaporthe oryzae invades the host via an appressorium specialized pressure-generating structure, which generates enormous turgor to penetrate host cuticles. However, due to the ongoing evolution of fungicide resistance, it is vitally essential to identify new targets and fungicides. Here, we showed that Trs85, a subunit of TRAPPIII complex, is essential for appressorium-mediated infection in M. oryzae. We explained how Trs85 regulates autophagy through Ypt1 (a small GTPase protein) in M. oryzae. We then identified a key conserved amphipathic α-helix within Trs85 associated with the pathogenicity of M. oryzae. Screening with the aid of the computer, we have identified a lead compound SP-141 that affects autophagy and Trs85-Ypt1 interaction. SP-141 demonstrates a substantial capacity to effectively inhibit the infection caused by the rice blast fungus, while also exhibiting a wide-ranging potential as an antifungal agent with broad-spectrum activity. Taken together, our data show that Trs85 is a potential new target and SP-141 has the potential for controlling rice blast. Our findings thus provide a novel strategy that may help humans fight against rice blast.