Inhibition of hepatitis C virus RNA replicons by peptide aptamers

Alla Trahtenherts, Meital Gal-Tanamy, Romy Zemel, Larisa Bachmatov, Shelly Loewenstein, Ran Tur-Kaspa, Itai Benhar

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Background/aims: Hepatitis C virus infection is a major worldwide health problem, causing chronic hepatitis, cirrhosis and primary liver cancer. In addition to its role in the viral polyprotein-processing, the viral NS3 serine protease has been implicated in interactions with various cell constituents resulting in phenotypic changes including malignant transformation. NS3 is currently regarded a prime target for anti-viral drugs thus specific inhibitors of its activities should be important. With the aim of inhibiting NS3 protease activity as a means to inhibit HCV replication we used a novel bacterial genetic screen to isolate NS3-inhibiting peptide aptamers. Methods: We have isolated and characterized seven NS3-inhibiting peptide aptamers. We investigated the phenotypic changes that SEAP-secreting subgenomic RNA replicons undergo upon intracellular expression of these peptide aptamers, assayed by real-time RT-PCR and inhibition of SEAP secretion by transfected replicon cells. Results and conclusions: The peptide aptamers inhibited NS3 protease activity in vitro with an IC50 in the low micromolar range. Upon transfection, aptamers inhibited the replication of SEAP-secreting genotype 1b subgenomic RNA replicons. Aptamer-based intracellular immunization may emerge as a promising antiviral approach to interfere with the life cycle and pathogenicity of HCV.

Original languageEnglish
Pages (from-to)195-205
Number of pages11
JournalAntiviral Research
Issue number3
StatePublished - Mar 2008
Externally publishedYes

Bibliographical note

Funding Information:
We thank Prof. Matti Sällberg (Karolinska Institutet, Stockholm, Sweden) for the 1a genotype-coding plasmid. We thank Prof. Stanley Lemon (The University of Texas Medical Branch, Galveston, Texas, USA) for the 1b genotype SEAP-secreting RNA replicons. This work was supported by a research grants from the Horowitz Fund, Israel and the Israel Cancer Association.


  • HCV
  • Liver diseases
  • NS3 serine protease
  • Peptide aptamers
  • RNA replicons


Dive into the research topics of 'Inhibition of hepatitis C virus RNA replicons by peptide aptamers'. Together they form a unique fingerprint.

Cite this