Hexapeptide functionality of cellulose as NS3 protease inhibitors.

Two novel groups of hexapeptide inhibitors for NS3 serine protease of the hepatitis C virus (HCV) are designed. The hexapeptide is an amino acid sequence of NS5A/NS5B substrate (Glu-Asp-Val-Val-Cys-Cys). In the first group, the hexapeptide binds to a cellulose monomer at the positions 2, 3 or 6 while in the second group, the hexapeptide binds to a cellulose dimmer at the positions 2, 3, 6, 2', 3' or 6'. Molecular modeling semiemprical PM3 calculations are used to optimize the geometry and calculate the electronic properties of the suggested inhibitors compared to that of natural substrate. Computational results show that the second group has the maximum stability and reactivity indicating that it would be considered as a promising HCV NS3 protease inhibitor.