From those eight derivatives the most promising inhibitors of the M pro enzyme are the derivatives ( ) and ( ), which have the best predicted free binding energies of -7.12 kcal/mol and -7.00 kcal/mol, respectively. Interestingly, these two derivatives are the only derivatives that possess an aromatic ring embedded in one of the tricyclic guanidine scaffolds. In general, there appears to be a correlation between the unsaturation in the tricyclic guanidine scaffold and the calculated binding score, e.g. the derivative ( ) is more unsaturated than its partner and has a predicted ∆GB lower than the predicted one for the derivative (11) (Table ).