The binding free energies of the protein-ligand complexes were evaluated in two ways. The traditional method is to calculate the energies of solvated SARS-CoV-2 helicase and small molecule ligands and that of the bound complex and derive the binding energy by subtraction. ΔG (binding, aq) = ΔG (complex, aq) -(ΔG (protein, aq) + ΔG (ligand, aq)