Interactions of ketoamide inhibitors on HCV NS3/4A protease target: molecular docking studies.
HCV infection in more than 200 million individuals worldwide is a principal health problem. Prior to the development of HCV protease inhibitor combination therapy, HCV infected patients were treated with pegylated interferon-α and ribavirin. The adverse side effects associated with this type of treatment may lead to the discontinuation of treatment in certain number of patients. Currently, the inhibitors of NS3/4A Protease were found promising candidates for the treatment of HCV infection. There are several inhibitors of HCV NS3/4A protease that are passing through clinical improvement showing good potency against HCV infections in a number of patients. To further recognize binding interactions and activity trend, the molecular docking studies were performed on a number of HCV NS3/4A protease ketoamide inhibitors via MOE docking protocol. The docking analysis resulted in the detection of important ligand interactions with respect to binding site of target protein and produced good correlation coefficient (r2 = 0.690) between docking score and biological activities. These molecular docking results should, in our view, contribute for further optimization of ketoamide derivatives as NS3/4A protease inhibitors.
Abdul
A
Wadood
Muhammad
M
Riaz
Syed Babar
SB
Jamal
Masaud
M
Shah
D000577:Amides / Q000737:chemistry; D000998:Antiviral Agents / Q000737:chemistry*; D001665:Binding Sites; D016174:Hepacivirus / Q000201:enzymology*; D006801:Humans; D062105:Molecular Docking Simulation; D011480:Protease Inhibitors / Q000737:chemistry*; D011485:Protein Binding; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000577:Amides; D000998:Antiviral Agents; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases