An update on small molecule inhibitors of the HCV NS5B polymerase: effects on RNA synthesis in vitro and in cultured cells, and potential resistance in viral quasispecies
S Chinnaswamy, H Cai, C Kao
Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, USA
Abstract: Chronic infection by the hepatitis C virus (HCV) can lead to liver cirrhosis and hepatocellular carcinoma. There is currently no prophylactic vaccine against HCV, and the treatment is currently limited to modified interferon and ribavirin. The RNA-dependent RNA polymerase (RdRp) of HCV is an attractive target for inhibitor development, and this has led to active efforts in the development of nucleoside and non-nucleoside inhibitors. The HCV polymerase is also one of the model systems for detailed analysis of how RdRp structure affects the mechanism of RNA synthesis. This review summarizes current efforts with inhibitors targeting the HCV RdRp and how the various inhibitors affect the mechanism of RNA synthesis.
Keywords: HCV infection, RdRp, nucleoside inhibitors, subgenomic replicons, ProTides, ribavirin, allosteric site
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF]
Other articles by this author:
Hoover HS, Kao CC
Published Date: 24 November 2016
Vaughan R, Running W, Qi R, Kao CC
Published Date: 2 May 2012
J Ortiz-Alcantara, K Bhardwaj, S Palaninathan, et al.
Published Date: 6 September 2010
Sreedhar Chinnaswamy, Ayaluru Murali, Hui Cai, et al
Published Date: 11 March 2010