In the Nirmatrelvir development the presence of the nitrile and pyrrolodine moieties was selected over a similar inhibitor with a benzothiazol-2-yl group to aid a reaction with cysteine 145. The pyrrolodine ring with the =O38 group and N36 is characteristic of both and the 2 high scores of O38 and nitrile N41 are characteristic of this mode. The nitrile shown in Figure forms a reversible covalent thioimidate adduct with CYS 145. In order for this covalent bond to form, the non-covalent binding has to be strong enough to draw the inhibitor into the pocket and also orient it to initiate the covalent reaction. The docking distribution of the total scoring has much to say about this and the states near the maximum binding.