Identification of Peptide Leads to Inhibit Hepatitis C Virus: Inhibitory Effect of Plectasin Peptide Against Hepatitis C Serine Protease
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The emerging of hepatitis C virus (HCV) resistant strains has been considered as a main drawback of the available drugs. Since HCV has a large inactive surface, we would like to hypothesis that the mutation occur in HCV is minimal and causing less resistance against inhibition. In this study, a short peptide inhibitor of HCV namely plectasin was identified by HCV NS3-4A serine protease assay. Plectasin peptide showed considerable inhibition against HCV NS3-4A serine protease. Enzymatic activity of the recombinant NS3-4Apro was analysed by fluorescence release from several fluorogenic peptide substrates which resembling the dibasic cleavage site sequences of the flavivirus polyprotein precursor. Of all amc-labelled peptides, Pyr-RTKR-amc was the most efficiently cleaved substrate with the lowest Km value of 20 µM. The kinetic assay showed that plectasin peptide inhibited NS3-4Apro activity with an IC50 value of 4.3 μM compared to the aprotinin as a standard proteases inhibitor with an IC50 of 6.1 μM. From the results, plectasin peptide also demonstrated a dose-dependent inhibition of HCV replication with a considerable reduction in RLuc activity at 15 µM using HCV replicon- containing Huh-7 cells. Our study has identified a unique natural peptide that can be used to highlight novel structures for the development of drug derivatives with high efficacy of HCV NS3-4A protease inhibitors.
KeywordsAntiviral peptide Plectasin Hepatitis C virus NS3-4A serine protease HCV replicon assay
This study was sponsored by the Ministry of Higher education/Malaysia through the University of Malaya, TRGS Grant (TR0001D-2014B).
Compliance with Ethical Standards
Conflict of Interest
Authors declare that they have no conflict of interest.
This article does not contain any study with human or animals performed by any of the authors.
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