Abstract
Based on the sequences of NS3/NS4A, NS4A/NS4B, NS4B/NS5A and NS5A/NS5B junctions, two groups of HCV NS3 protease inhibitors are suggested. The first group has neutral compounds, while the second group has charged compounds. Each group has tetrapeptides, hexapeptides and macrocyclic structures. Using PM3 method, the electronic and QSAR properties are calculated. Accordingly, P1-P3 macrocycle of 4A/4B hexapeptide sequence (DEMEEC) is the most stable and hydrophilic in the first group. While the charged compounds in second group are more reactive and soluble than first group. The best compound and its charged counterpart are further studied at B3LYP/6-31G (d, p) and HF/6-31G (d, p) methods. The difference in position and energies of HOMO and LUMO between the two compounds infers different mechanisms of action between them and they react differently from a chemical point of view. These two compounds are well suited to be good inhibitors of HCV NS3 protease.