This is probably due to the fact that the active site is flat and negatively charged, which might lead to a weak binding of the inhibitor to the enzyme [24] and [25]. One accepted NS2B/NS3pro inhibitor is aprotinin, which envelops the enzyme and prevents the substrate from accessing the protease active site [12]. From various published studies on the activity of NS2B/NS3pro [26], [27] and [28], the preferential substrate contains basic residues (R or K) at the P1 and P2 sites and a short side-chain amino acid (G, S or A) at the P1′ site [29] and [30], where the protease cleaves at the P2P1↓P1′ sites.