However, some care must be taken in this analysis as the same trend is not obtained for the more unsaturated derivative ( ) and its partner (3). The hydroxyl substituent in the position R 4 or R 5 also appears to improve the calculated binding score, e.g. the derivative (8) with a N-OH group has a predicted ∆GB lower than that predicted for its partner with a N-H group. The same trend was obtained for the two tricyclic guanidine derivatives and . The chemical structure of the most promising derivatives ( ) and ( ) differs in the position of the hydroxyl group in the tricyclic guanidine core, at the R 4 or R 5 positions. The calculated binding score is improved for the derivative with a hydroxyl group at the R 4 position (Figure ). To compare the structural similarity between guanidine-containing derivatives (1-15), and the known inhibitors of the M pro enzyme, O6k and N3, the Tanimoto similarity scores (TSS) between them were calculated.