期刊
INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS
卷 23, 期 2, 页码 163-170出版社
SPRINGER
DOI: 10.1007/s10989-016-9544-6
关键词
Antiviral peptide; Plectasin; Hepatitis C virus; NS3-4A serine protease; HCV replicon assay
资金
- Ministry of Higher education/Malaysia through the University of Malaya, TRGS Grant [TR0001D-2014B]
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 A mu M. The kinetic assay showed that plectasin peptide inhibited NS3-4Apro activity with an IC50 value of 4.3 mu M compared to the aprotinin as a standard proteases inhibitor with an IC50 of 6.1 mu M. From the results, plectasin peptide also demonstrated a dose-dependent inhibition of HCV replication with a considerable reduction in RLuc activity at 15 A mu M 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.
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