Structures of 13 inhibitors of the main protease (M pro ) of SARS-CoV-2 were built using the FEgrow workflow and taken through to free energy calculations for accurate physics-based scoring. The PDB structure, 7L10, was used for the receptor, missing residues (E47 and D48) were added using MODELLER and hydrogen atoms were added using Chimera. The BioSimSpace package was used for free energy setup, along with a relative binding free energy protocol described previously. In brief, the lowest energy conformer for each ligand was parameterised with the GAFF2 force field. The AMBER FF14SB 39 force field was used for the protein, along with the TIP3P water model. Each ligand was then solvated in a 35 Å cube, or 90 Å cube in the presence of the protein. The bound and unbound structures then underwent a short equilbration in the NpT ensemble at 300 K.