New NS5B polymerase inhibitors for hepatitis C

Expert Opinion on Investigational Drugs
Florence Legrand-AbravanelJacques Izopet

Abstract

The current treatment of chronic hepatitis C based on the combination of pegylated interferon and ribavirin is effective in only 50% of patients. Specific targeted antiviral therapies represent a promising approach to eradicate the infection. This review focuses on progress towards the development of the hepatitis C virus (HCV) polymerase inhibitors that have entered clinical development in recent years. Nucleos(t)ide analogues target the active site of the HCV polymerase and acts as chain terminators. They have similar activity against all genotypes and the virus has a high genetic barrier to drug resistance. Non-nucleoside inhibitors achieve polymerase inhibition by binding to one of the at least four allosteric enzyme sites. Most of them have a genotype-specific activity and they may select rapidly drug-resistant variants if HCV replication is not completely suppressed. Nonetheless, they provide additional options for addressing the needs of infected patients. NS5B polymerase inhibitors will form an integral part of more effective anti-HCV therapy, in combination with interferon or with other directly acting antiviral agents.

References

Nov 11, 1999·Proceedings of the National Academy of Sciences of the United States of America·S BressanelliF A Rey
Jun 22, 2000·The Journal of General Virology·R Bartenschlager, V Lohmann
Apr 28, 2001·Journal of Clinical Microbiology·P HalfonD Ouzan
Sep 27, 2002·The New England Journal of Medicine·Michael W FriedJian Yu
Apr 25, 2003·Journal of Virological Methods·K Sandres-SaunéJ Izopet
Dec 14, 2004·Journal of Medicinal Chemistry·Ariamala GopalsamyJohn O'Connell
Dec 18, 2004·The Journal of General Virology·Florence NicotJacques Izopet
May 3, 2005·Bioorganic & Medicinal Chemistry Letters·Jeffrey A PfefferkornFrancis J Schwende
May 25, 2005·Bioorganic & Medicinal Chemistry Letters·Jeffrey A PfefferkornFrancis J Schwende
Jun 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jin ZhongFrancis V Chisari
Sep 9, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Peter SimmondsAnders Widell
Oct 27, 2005·Nucleosides, Nucleotides & Nucleic Acids·C PierraG Gosselin
Jan 28, 2006·Biochemical and Biophysical Research Communications·Anna M Boguszewska-ChachulskaMaria Bretner
Jun 8, 2006·Journal of Clinical Microbiology·Jean-François CantaloubePhilippe de Micco
Jul 11, 2006·Bioorganic & Medicinal Chemistry Letters·Hui LiShella Fuhrman
Apr 27, 2007·Journal of Virology·Frederik PauwelsKenneth A Simmen
May 10, 2007·Nature Reviews. Microbiology·Darius MoradpourCharles M Rice
Aug 8, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tara L KiefferStefan Zeuzem
Sep 20, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nicole ForestierStefan Zeuzem
Apr 5, 2008·Drug News & Perspectives·Richard L MillerMark A Tomai
Jun 24, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Paul J PockrosGeorge Hill
Sep 18, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jessica D KormanUNKNOWN Pediatric and Adult Acute Liver Failure Study Groups
Oct 17, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jennifer A TanSammy Saab
Nov 26, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Thomas KuntzenTodd M Allen
Dec 17, 2008·Antimicrobial Agents and Chemotherapy·Steven S CarrollDavid B Olsen
May 19, 2009·Journal of Hepatology·Curtis CooperLouise Proulx

❮ Previous
Next ❯

Citations

Oct 15, 2013·Journal of Chemical Information and Modeling·Khaled H BarakatMichael Houghton
Jul 19, 2011·Journal of Medicinal Chemistry·Rui LiuGang Liu
Sep 28, 2013·Journal of Medicinal Chemistry·Ryan C SchoenfeldJunping Zhao
Dec 19, 2013·Journal of Medicinal Chemistry·Tim H M JonckersPierre Raboisson
Feb 24, 2012·Nucleosides, Nucleotides & Nucleic Acids·Fabio CasuGiuseppe Gumina
Sep 17, 2010·Journal of Clinical Microbiology·Dimitry GryadunovJacques Izopet
Jun 29, 2011·Future Medicinal Chemistry·Maria Letizia BarrecaVioletta Cecchetti
Nov 28, 2013·Antiviral Research·Steven J CoatsRaymond F Schinazi
Jun 6, 2014·European Journal of Gastroenterology & Hepatology·Adrian M Di BisceglieMargaret J Koziel
Nov 13, 2012·Annual Review of Pharmacology and Toxicology·Jennifer J Kiser, Charles Flexner
May 23, 2014·Expert Opinion on Investigational Drugs·Ivan GentileGuglielmo Borgia
Jul 3, 2013·Journal of the Formosan Medical Association = Taiwan Yi Zhi·Yi-Hao YenChuan-Mo Lee
Mar 24, 2012·Current Opinion in Virology·Priscilla L YangValerie A Villareal
Jan 11, 2012·Liver International : Official Journal of the International Association for the Study of the Liver·Sandra Bühler, Ralf Bartenschlager
Dec 3, 2014·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Marc BourlièrePaul Castellani
Dec 3, 2014·Journal of Hepatology·Sonal Kumar, Ira M Jacobson
Jan 25, 2011·Journal of Molecular Biology·Celia PeralesEsteban Domingo
Apr 3, 2013·Bioorganic & Medicinal Chemistry Letters·Timothy A StammersPierre L Beaulieu
Jan 8, 2013·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Yasir WaheedMuhammad Ashraf
Sep 22, 2012·Antiviral Research·Christian G Noble, Pei-Yong Shi
Apr 1, 2014·Methods : a Companion to Methods in Enzymology·Eleni VrontakiAntreas Afantitis
May 4, 2016·Expert Opinion on Drug Metabolism & Toxicology·Onyema OgbuaguR Douglas Bruce
May 31, 2016·Journal of Biomolecular Structure & Dynamics·Bodee NuthoThanyada Rungrotmongkol
May 15, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jianwei ShenVolker Fischer
Jan 18, 2012·Journal of Medicinal Chemistry·Kevin X ChenF George Njoroge

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.