Searching for Novel Targets to Control Wheat Head Blight Disease—I-Protein Identification, 3D Modeling and Virtual Screening

International audienceFusarium head blight (FHB) is a destructive disease of wheat and other cereals. FHBoccurs in Europe, North America and around the world causing significant losses inproduction and endangers human and animal health. In this article, we provide thestrategic steps for the specific target selection for the phytopathogen system wheat-Fusarium graminearum. The economic impact of FHB leads to the need for innovation.Currently used fungicides have been shown to be effective over the years, butrecently cereal infecting Fusaria have developed resistance. Our work presents a newperspective on target selection to allow the development of new fungicides. We developedan innovative approach combining both genomic analysis and molecularmodeling to increase the discovery for new chemical compounds with both safetyand low environmental impact. Our protein targets selection revealed 13 candidateswith high specificity, essentiality and potentially assayable with a favorable accessibilityto drug activity. Among them, three proteins: trichodiene synthase, endoglucanase-5 and ERG6 were selected for deeper structural analyses to identify new putativefungicides. Overall, the bioinformatics filtering for novel protein targets appliedfor agricultural purposes is a response to the demand for chemical crop protection.The availability of the genome, secretome and PHI-base allowed the enrichment ofthe search that combined experimental data in planta . The homology modeling andmolecular dynamics simulations allowed the acquisition of three robust and stableconformers. From this step, approximately ten thousand compounds have been virtuallyscreened against three candidates. Forty-five top-ranked compounds were selectedfrom docking results as presenting better interactions and energy at the bindingpockets and no toxicity. These compounds may act as inhibitors and lead to thedevelopment of new fungicides