Translational Approach with AI for Klebsiella Drug Discovery

Marisa Fabiana Nicolás of the National Laboratory for Scientific Computing in Brazil, alongside other research groups in Brazil and collaborators from Argentina, Chile, Mexico, Uruguay, Canada, and Portugal, will lead an interdisciplinary project to discover and validate small-molecule inhibitors targeting Klebsiella pneumoniae proteins. The team will integrate supercomputing, AI-driven modeling, CRISPRi knockdowns, Ribo-seq, enzymatic, and structural assays to identify high-value bacterial targets and generate validated small-molecule inhibitors. Target prioritization will be performed using the Target-Pathogen platform. Selected high-priority targets will be validated using CRISPRi strains, followed by virtual screening with DockThor-VS and rational design via DockTDesign to identify and optimize novel compounds. Hit compounds will be synthesized, tested in vitro, and evaluated through structure-activity relationship (SAR) analysis and on-target validation experiments to confirm antibacterial activity and target engagement. The ultimate goal is to deliver validated lead compounds with strong therapeutic potential against multidrug-resistant K. Pneumoniae.