Mechanistic characterization of GS-9190 (tegobuvir), a novel nonnucleoside inhibitor of hepatitis C virus NS5B polymerase

Antimicrobial Agents and Chemotherapy

Volumn 55, Issue 9, 2011, Pages 4196-4203

  Shih, I Hung ^a   Vliegen, Inge ^b   Peng, Betty ^a   Yang, Huiling ^a   Hebner, Christy ^a   Paeshuyse, Jan ^b   Pürstinger, Gerhard ^c   Fenaux, Martijn ^a   Tian, Yang ^a   Mabery, Eric ^a   Qi, Xiaoping ^a   Bahador, Gina ^a   Paulson, Matthew ^a   Lehman, Laura S ^a   Bondy, Steven ^a   Tse, Winston ^a   Reiser, Hans ^a   Lee, William A ^a   Schmitz, Uli ^a   Neyts, Johan ^b   Zhong, Weidong ^a   more..

^a GILEAD SCIENCES   (United States)

^b REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^c UNIVERSITY OF INNSBRUCK   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

A 782759; ANTIVIRUS AGENT; CILUPREVIR; GT1B PROTEIN; GT2A PROTEIN; NESBUVIR; NONSTRUCTURAL PROTEIN 5B; TEGOBUVIR; UNCLASSIFIED DRUG; VIRUS PROTEIN;

ANTIVIRAL ACTIVITY; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CONTROLLED STUDY; CROSS RESISTANCE; CYTOTOXICITY; DRUG STRUCTURE; GENOTYPE; HEPATITIS C VIRUS; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REPLICON; VIRUS INHIBITION; VIRUS MUTATION; VIRUS REPLICATION; VIRUS RESISTANCE;

ANTIVIRAL AGENTS; CELL LINE; ENZYME INHIBITORS; HEPACIVIRUS; HUMANS; MOLECULAR STRUCTURE; MUTATION; PLASMIDS; VIRAL NONSTRUCTURAL PROTEINS;

EID: 80051820156     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00307-11     Document Type: Article

References (40)

1. Bavisotto, L., et al. 2007. Antiviral, pharmacokinetic and safety data for GS-9190, a non-nucleoside HCB NS5B polymerase inhibitor, in a phase-1 trial in HCB genotype 1 infected subjects. Hepatology 46(Suppl. 1):255A.
2. Behrens, S E, L. Tomei, and R. De Francesco. 1996. Identification and properties of the RNA-dependent RNA polymerase of hepatitis C virus. EMBO J. 15:12-22. (Pubitemid 26020384)
3. Biswal, B K, et al. 2005. Crystal structures of the RNA-dependent RNA polymerase genotype 2a of hepatitis C virus reveal two conformations and suggest mechanisms of inhibition by non-nucleoside inhibitors. J. Biol. Chem. 280:18202-18210. (Pubitemid 41389065)
4. Carroll, S S, et al. 2003. Inhibition of hepatitis C virus RNA replication by 2′-modified nucleoside analogs. J. Biol. Chem. 278:11979-11984. (Pubitemid 36800172)
5. Chun, Y J, et al. 2009. Potent inhibition of human cytochrome P450 1B1 by tetramethoxystilbene. Toxicol. Lett. 189:84-89.
6. Eldrup, A B, et al. 2004. Structure-activity relationship of purine ribonucleosides for inhibition of hepatitis C virus RNA-dependent RNA polymerase. J. Med. Chem. 47:2283-2295. (Pubitemid 38478852)
7. Fleischer, R., D. Boxwell, and K E Sherman. 2004. Nucleoside analogues and mitochondrial toxicity. Clin. Infect. Dis. 38:e79-e80.
8. Fried, M W, et al. 2002. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N. Engl. J. Med. 347:975-982.
9. Gane, E J, et al. 2010. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): A randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet 376:1467-1475.
10. Hezode, C., et al. 2009. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N. Engl. J. Med. 360:1839-1850.
11. Hodson, P V, K. Qureshi, C A Noble, P. Akhtar, and R S Brown. 2007. Inhibition of CYP1A enzymes by alpha-naphthoflavone causes both synergism and antagonism of retene toxicity to rainbow trout (Oncorhynchus mykiss). Aquat. Toxicol. 81:275-285. (Pubitemid 46273700)
12. Hung, M., C S Gibbs, and M. Tsiang. 2002. Biochemical characterization of rhinovirus RNA-dependent RNA polymerase. Antiviral Res. 56:99-114. (Pubitemid 35279660)
13. Kneteman, N M, et al. 2009. HCV796: A selective nonstructural protein 5B polymerase inhibitor with potent anti-hepatitis C virus activity in vitro, in mice with chimeric human livers, and in humans infected with hepatitis C virus. Hepatology 49:745-752.
14. Kwo, P., et al. 2009. 44th Annu. Meet. Eur. Assoc. Study Liver, Copenhagen, Denmark, 22 to 26 April 2009, abstr. 4. European Association for the Study of the Liver, Geneva, Switzerland.
15. Lai, V C, S. Dempsey, J Y Lau, Z. Hong, and W. Zhong. 2003. In vitro RNA replication directed by replicase complexes isolated from the subgenomic replicon cells of hepatitis C virus. J. Virol. 77:2295-2300. (Pubitemid 36110046)
16. Lam, A M, et al. 2010. PSI-7851, a pronucleotide of β-D-2′- deoxy-2′-fluoro-2′-C-methyluridine monophosphate: A potent and pan-genotype inhibitor of hepatitis C virus replication. Antimicrob. Agents Chemother. 54:3187-3196.
17. Lamarre, D., et al. 2003. An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus. Nature 426:186-189. (Pubitemid 37442587)
18. Le Pogam, S., et al. 2010. RG7128 alone or in combination with pegylated interferon-α2a and ribavirin prevents hepatitis C virus (HCV) replication and selection of resistant variants in HCV-infected patients. J. Infect. Dis. 202:1510-1519.
19. Lesburg, C A, et al. 1999. Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site. Nat. Struct. Biol. 6:937-943. (Pubitemid 29463307)
20. Lohmann, V., F. Korner, U. Herian, and R. Bartenschlager. 1997. Biochemical properties of hepatitis C virus NS5B RNA-dependent RNA polymerase and identification of amino acid sequence motifs essential for enzymatic activity. J. Virol. 71:8416-8428. (Pubitemid 27446422)
21. Lohmann, V., et al. 1999. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285:110-113. (Pubitemid 29307577)
22. Madan, A., A. Parkinson, and M D Faiman. 1993. Role of flavin-dependent monooxygenases and cytochrome P450 enzymes in the sulfoxidation of S-methyl N,N-diethylthiolcarbamate. Biochem. Pharmacol. 46:2291-2297. (Pubitemid 24012322)
23. Manns, M P, et al. 2001. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: A randomised trial. Lancet 358:958-965. (Pubitemid 32913521)
24. Mo, H., et al. 2005. Mutations conferring resistance to a hepatitis C virus (HCV) RNA-dependent RNA polymerase inhibitor alone or in combination with an HCV serine protease inhibitor in vitro. Antimicrob. Agents Chemother. 49:4305-4314. (Pubitemid 41400978)
25. Nguyen, T T, et al. 2003. Resistance profile of a hepatitis C virus RNA-dependent RNA polymerase benzothiadiazine inhibitor. Antimicrob. Agents Chemother. 47:3525-3530. (Pubitemid 37345714)
26. Olsen, D B, et al. 2004. A 7-deaza-adenosine analog is a potent and selective inhibitor of hepatitis C virus replication with excellent pharmacokinetic properties. Antimicrob. Agents Chemother. 48:3944-3953. (Pubitemid 39304626)
27. Paulson, M., et al. 2008. Int. Symp. Hepatitis C Virus Rel. Vir., San Antonio, TX, 5 to 9 October 2008, abstr. 023. ICMS Pty, Ltd., Southbank, Victoria, Australia.
28. Puerstinger, G., et al. 2006. Substituted 5-benzyl-2-phenyl-5H-imidazo[4, 5-c]pyridines: A new class of pestivirus inhibitors. Bioorg. Med. Chem. Lett. 16:5345-5349. (Pubitemid 44332215)
29. Robinson, M., et al. 2010. Novel hepatitis C virus reporter replicon cell lines enable efficient antiviral screening against genotype 1a. Antimicrob. Agents Chemother. 54:3099-3106.
30. Sarrazin, C, and S. Zeuzem. 2010. Resistance to direct antiviral agents in patients with hepatitis C virus infection. Gastroenterology 138:447-462.
31. Shi, S T, et al. 2009. Preclinical characterization of PF-00868554, a potent nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase. Antimicrob. Agents Chemother. 53:2544-2552.
32. Simmonds, P. 2004. Genetic diversity and evolution of hepatitis C virus: 15 years on. J. Gen. Virol. 85:3173-3188. (Pubitemid 39445434)
33. Targett-Adams, P., et al. 2011. Small molecules targeting hepatitis C virus-encoded NS5A cause subcellular redistribution of their target: Insights into compound mode of action. J. Virol. 85:6353-6358.
34. Villano, S A, et al. 2007. Antiviral activity of the non-nucleoside polymerase inhibitor, HCV-796, in combination with pegylated interferon alfa-2b in treatment-naive patients with chronic HCV. J. Hepatol. 46:S24.
35. Vliegen, I., et al. 2009. Substituted imidazopyridines as potent inhibitors of HCV replication. J. Hepatol. 50:999-1009.
36. Wasley, A, and M J Alter. 2000. Epidemiology of hepatitis C: Geographic differences and temporal trends. Semin. Liver Dis. 20:1-16. (Pubitemid 30421405)
37. Yamashita, T., et al. 1998. RNA-dependent RNA polymerase activity of the soluble recombinant hepatitis C virus NS5B protein truncated at the C-terminal region. J. Biol. Chem. 273:15479-15486. (Pubitemid 28298156)
38. Yang, H, and W E Delaney IV. 2006. A novel fluorescence-based protease assay using the endogenous NS3/4A protease activity present in the total cell lysates of HCV replicon cells. J. Clin. Virol. 36:S109-S110.
39. Zeuzem, S., et al. 2010. 60th Annu. Meet. Am. Assoc. Study Liver Dis., abstr. LB-1. Boston, MA, 29 October to 2 November 2010. American Association for the Study of Liver Diseases, Alexandria, VA.
40. Zhong, W., et al. 2000. Template/primer requirements and single nucleotide incorporation by hepatitis C virus nonstructural protein 5B polymerase. J. Virol. 74:9134-9143.