Fig. 4.

Structure-enabled machine learning identified multiple, more potent ligands in a small number of synthesized compounds. We applied the model to design a reductive amination library (A) and amidation library (B), which is screened against the main protease inhibition using a fluorescence assay. The library is designed to extend into the untapped P1’ binding pocket of the active site. The structure shown is Mpro-x11498 from Diamond/XChem (35).