We also analyzed the chemical scaffolds of Bemis and Murcko on 217 active compounds against the S. aureus dataset (STADS) . The top 25% most active compounds against S. aureus FabI were selected from the 217 compounds in the STADS, based on the third quartile (Q3) of the pIC50 value distribution. This subset consisted of 59 inhibitors, for which their respective Murcko SMILES were determined by the RDKit module to calculate scaffold frequency. The most frequently identified framework was (9-benzyl-1,3,4,9-tetrahydro-2H-pyrido indol-2-yl)(phenyl)methanone (Entry 1, Supplementary Data Table ), followed by diaryl ether (Entry 2, Supplementary Data Table ) and 5-phenoxy-2-(phenoxymethyl)pyridin-4(1H)-one (Entry 3, see Supplementary Table ). Notably, these scaffolds represent some of the most potent inhibitors reported in the literature, such as 2, evaluated in a Phase I clinical trial, and 3 and 4, with high IC50 values of 0.1 μM and 0.08 μM, respectively (Figure ).