From Genome Inspection to Precision Agrochemicals: A Structure-Based Antivirulence Roadmap for Sustainable Crop Protection against Xylella fastidiosa

: The emergence of antimicrobial resistance and environmental concerns is driving the need for sustainable crop-protection strategies beyond conventional pathogen-killing approaches. Here, we outline a structure-based drug discovery (SBDD) framework tailored to Xylella fastidiosa, one of the most threatening bacterial plant pathogens worldwide. By adapting conceptual and methodological pillars from human drug discovery, our approach focuses on antivirulence strategies that target pathogenicity factors rather than on bacterial viability. We provide a rational discovery roadmap encompassing genomic analysis, target assessment, in silico identification of candidate agrochemicals, and experimental multilevel validation in vitro and in planta. Building on this, our paper offers both theoretical background and practical recommendations to accelerate the identification of safe and effective crop protectors against Xylella fastidiosa, ultimately supporting the development of more sustainable and evolutionarily robust plant-disease-management strategies.