Fig. 4. Binding poses and cellular activities of SpotXplorer0 hits against challenging and current targets.

a Predicted binding pose of the fragment SX045 (green) in the binding pocket of the SETD2 histone methyltransferase. The fragment decreases the viability of MV4-11 and MOLM-13 leukemia cells in a dose-dependent manner (see Supplementary Information, section 8), with IC₅₀ values of 400 µM and 333 µM, respectively. b X-ray structure of the fragment SX013 in complex with the main protease (3CLPro) of the SARS-CoV-2 virus (PDB entry 5RHD). The fragment inhibits the SARS-COV-2-induced mortality of Vero E6 cells with an EC₅₀ of 304 µM. c X-ray structures of fragments SX005, SX048 and SX051 (left to right) in complex with the NSP3 macrodomain of the SARS-CoV-2 virus (PDB entries 5S4G, 5S4H, and 5S4I). The fragments show antiviral activities with EC₅₀ values in the high micromolar range in the cellular assay. (In the IC₅₀ and EC₅₀ plots, data are presented as mean values +/− SD, calculated from n = 3 biologically independent samples.) Source data are provided in the Source Data file.