Identification of Peptide Leads to Inhibit Hepatitis C Virus: Inhibitory Effect of Plectasin Peptide Against Hepatitis C Serine Protease

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 shor...

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Bibliographic Details
Published in:International journal of peptide research and therapeutics 2017-06, Vol.23 (2), p.163-170
Main Authors: Abdulrahman, Ammar Y., Rothan, Hussin A., Rashid, Nurshamimi Nor, Lim, See Khai, Sakhor, Wajihah, Tee, Kah Ching, Teoh, Teow Chong, Rahman, Noorsaadah A., Yusof, Rohana
Format: Article
Language:English
Subjects:
Animal Anatomy
Antiviral drugs
Biochemistry
Biomedical and Life Sciences
Flavivirus
Hepatitis
Hepatitis C
Hepatitis C virus
Histology
Life Sciences
Molecular Medicine
Morphology
Peptides
Pharmaceutical Sciences/Technology
Pharmacology/Toxicology
Polymer Sciences
Proteases
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Summary: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 IC 50 value of 4.3 μM compared to the aprotinin as a standard proteases inhibitor with an IC 50 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.
ISSN:1573-3149
1573-3904
DOI:10.1007/s10989-016-9544-6