Fig 1: (A) The predicted binding poses of VPC285785 (cyan), VPC285786 (pink), Nirmatrelvir (yellow) and 4IT (orange) by covalent docking to Mpro (PDB:7R7H). Glu166 appears multiple times due to it possessing multiple strong interactions with the ligands. His41 and His163 are labelled as the Nε tautomer (Hie) or charged species (Hip), respectively, since the docking requires explicit hydrogens. The lowest energy protonation structure of the protein is calculated during the docking workflow. (B) Structures of compounds investigated in this study. (C) The predicted binding poses of Nirmatrelvir (yellow), VPC285785 (cyan), VPC285786 (pink) and XU3 (orange) to CatL (PDB: 2XU3, His163 is labelled as Hie). Images A and C were generated using Molecular Operating Environment (MOE v2020, www.chemcomp.com). Image B was created in ChemDraw Professional v23.0.1.10 (RevvitySignals, https://revvitysignals.com/products/research/chemdraw).
Fig 2: (A) Mpro IC50 curves for Nirmatrelvir, VPC285785 and VPC285786 using a fluorescent substrate assay. (B) dissociation constant (KD) as measured by microscale thermophoresis (MST). (C) CatL IC50 curves for VPC285786 using a fluorescent substrate assay. Nirmatrelvir and VPC285785 displayed little or no inhibition at or above 10 µM and were not quantified further.
Supplier Page from Abcam for Cathepsin L Inhibitor Assay Kit (Fluorometric)