Foot and mouth disease leader protease (Lbpro): Investigation of prime side specificity allows the synthesis of a potent inhibitor

► Lbpro is a small papain-like cysteine peptidase but has prime side specificity at least down to the S5′ site. ► S1 and S1′ specificities depend on their occupancy allowing cleavages at K↓G, R↓G or G↓R bonds but not at K-R. ► Like other cysteine peptidases proline was very well accepted by S2′ site of Lbpro. ► Lbpro potent inhibitor derived E64 was synthesized, E64-R-P-NH2.