Furthermore, there are generally more bi-modal distributions in the highest scoring covalently bound conformation than the non-covalent, as seen in the color coded Figures and. There is less flexibility in the covalently bound highest scoring conformation and as a result there is more specificity just by less room for the molecule to flex into. Any structural modifications of Nirmatrelvir could benefit from detailed knowledge of the atomic score distributions in both binding poses. Note that O27 is almost zero in interaction as it was in the non-covalent analysis. Atom O27 is not interactive in Nirmatrelvir. It has no role in interaction with Mpro as far as binding is concerned.