All known proteases have been classified in four classes and many subgroups according to three parameters: (i) their catalytic center, (ii) their substrate specificity, and (iii) their three-dimensional structure. The classification of the different picornavirus proteases initially relied upon the effect of protease inhibitors. Compounds that blocked sulphydryl groups abrogated the proteolytic activity of 2A pro and 3C pro , suggesting that the nucleophilic aminoacid in the active site was cysteine [54, 55] . However, another cysteine inhibitor such as E64 had no effect on these proteases, while L pro activity was inhibited not only by sulphydrylactive compounds but also by E64 [56, 57] . These findings together with structural observations imply that L pro belongs to the class of papain-like cysteine proteinases [43, [58] [59] [60] . Comparison of the structure of picornavirus proteases with prototypes of cellular ones revealed that both 2A pro and 3C pro are similar in structure to the chymotrypsin like group [61] [62] [63] . Picornavirus 3C pro reflects similarities to the staphylococcus aureus proteinase, whereas 2A pro is more akin to streptomyces griseus proteinase A.