Inhibition of hepatitis C virus RNA replicons by peptide aptamers.

@article{citeulike:2793604, abstract = {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.}, address = {Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Green Building, Tel-Aviv University, 69978 Ramat Aviv, Israel.}, author = {Trahtenherts, A. and Gal-Tanamy, M. and Zemel, R. and Bachmatov, L. and Loewenstein, S. and Tur-Kaspa, R. and Benhar, I. }, citeulike-article-id = {2793604}, doi = {10.1016/j.antiviral.2007.12.013}, issn = {0166-3542}, journal = {Antiviral research}, month = {March}, number = {3}, pages = {195--205}, posted-at = {2008-05-13 06:34:51}, priority = {2}, title = {Inhibition of hepatitis C virus RNA replicons by peptide aptamers.}, url = {http://dx.doi.org/10.1016/j.antiviral.2007.12.013}, volume = {77}, year = {2008} }

TY - JOUR ID - citeulike:2793604 L3 - citeulike-article-id:2793604 TI - Inhibition of hepatitis C virus RNA replicons by peptide aptamers. JF - Antiviral research VL - 77 IS - 3 SP - 195 EP - 205 AD - Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Green Building, Tel-Aviv University, 69978 Ramat Aviv, Israel. SN - 0166-3542 N2 - 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. AU - Trahtenherts, A AU - Gal-Tanamy, M AU - Zemel, R AU - Bachmatov, L AU - Loewenstein, S AU - Tur-Kaspa, R AU - Benhar, I PY - 2008/03// UR - http://dx.doi.org/10.1016/j.antiviral.2007.12.013 ER -