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- Title
Molecular Modeling Comparison of the Performance of NS5b Polymerase Inhibitor (PSI-7977) on Prevalent HCV Genotypes.
- Authors
Elfiky, Abdo; Elshemey, Wael; Gawad, Wissam; Desoky, Omar
- Abstract
The current available treatment for hepatitis C virus (HCV)-the causative of liver cirrhosis and development of liver cancer-is a dual therapy using modified interferon and ribavirin. While this regimen increases the sustained viral response rate up to 40-80 % in different genotypes, unfortunately, it is poorly tolerated by patients. PSI-7977, a prodrug for PSI-7409, is a Non-Structural 5b (NS5b) polymerase nucleoside inhibitor that is currently in phase III clinical trials. The activated PSI-7977 is a direct acting antiviral (DAA) drug that acts on NS5b polymerase of HCV through a coordination bond with the two Mg present at the GDD active site motif. The present work utilizes a molecular modeling approach for studying the interaction between the activated PSI-7977 and the 12 amino acids constituting a 5 Å region surrounding the GDD active triad motif for HCV genotypes 1a, 2b, 3b and 4a. The analysis of the interaction parameters suggests that PSI-7977 is probably a better DAA drug for HCV genotypes 1a and 3b rather than genotypes 2b and 4a.
- Subjects
MOLECULAR models; COMPARATIVE studies; POLYMERASES; CHEMICAL inhibitors; HEPATITIS C prevention; VIRAL genetics; CIRRHOSIS of the liver
- Publication
Protein Journal, 2013, Vol 32, Issue 1, p75
- ISSN
1572-3887
- Publication type
Article
- DOI
10.1007/s10930-013-9462-9