In vitro activity and resistance profile of samatasvir, a novel NS5A replication inhibitor of hepatitis C virus

Antimicrobial Agents and Chemotherapy

Volumn 58, Issue 8, 2014, Pages 4431-4442

  Bilello, J P ^a   Lallos, L B ^a   McCarville, J F ^a   La Colla, M ^a   Serra, I ^a   Chapron, C ^a   Gillum, J M ^a   Pierra, C ^a   Standring, D N ^a   Seifer, M ^a  

^a Idenix Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; ANTIVIRUS AGENT; BENZIMIDAZOLE DERIVATIVE; CARBAMIC ACID DERIVATIVE; GUANOSINE PHOSPHATE; IDX 184; NS-5 PROTEIN, HEPATITIS C VIRUS; NS3 PROTEIN, HEPATITIS C VIRUS; RIBAVIRIN; SAMATASVIR; VIRUS PROTEIN;

ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS; ANTIVIRAL RESISTANCE; CELL LINE; DOSE RESPONSE; DRUG EFFECTS; DRUG POTENTIATION; GENE EXPRESSION REGULATION; GENETICS; GENOTYPE; GROWTH, DEVELOPMENT AND AGING; HEPACIVIRUS; HEPG2 CELL LINE; HUMAN; METABOLISM; MUTATION; REPLICON; VIRUS REPLICATION;

ANTIVIRAL AGENTS; BENZIMIDAZOLES; CARBAMATES; CELL LINE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG RESISTANCE, VIRAL; DRUG SYNERGISM; GENE EXPRESSION REGULATION, VIRAL; GENOTYPE; GUANOSINE MONOPHOSPHATE; HEP G2 CELLS; HEPACIVIRUS; HUMANS; INTERFERON-ALPHA; MUTATION; REPLICON; RIBAVIRIN; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION;

EID: 84905400652     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.02777-13     Document Type: Article

References (49)

1. Burke KP, Cox AL. 2010. Hepatitis C virus evasion of adaptive immune responses: a model for viral persistence. Immunol. Res. 47:216-227. http://dx.doi.org/10.1007/s12026-009-8152-3.
2. Vertex Pharmaceuticals, Inc. 2011. Incivek (telaprevir) package insert. Vertex Pharmaceuticals, Cambridge, MA. http://www.accessdata.fda.gov/drugsatfda- docs/label/2011/201917lbl.pdf.
3. Zeuzem S, Berg T, Moeller B, Hinrichsen H, Mauss S, Wedemeyer H, Sarrazin C, Hueppe D, Zehnter E, Manns MP. 2009. Expert opinion on the treatment of patients with chronic hepatitis C. J. Viral Hepat. 16:75-90. http://dx.doi.org/10.1111/j.1365-2893.2008.01012.x.
4. Lange CM, Sarrazin C, Zeuzem S. 2010. Review article: specifically targeted anti-viral therapy for hepatitis C-a new era in therapy. Aliment. Pharmacol. Ther. 32:14-28. http://dx.doi.org/10.1111/j.1365-2036.2010.04317.x.
5. Gilead Sciences, Inc. 2013. Sovaldi (sofosbuvir) package insert. Gilead Sciences, Inc., Foster City, CA. http://www.gilead.com/+/media/Files/pdfs/ medicines/liver-disease/sovaldi/sovaldi-pi.pdf.
6. Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky JM. 2004. Structural biology of hepatitis C virus. Hepatolog. 39:5-19. http://dx.doi.org/10.1002/ hep.20032.
7. He Y, Staschke KA, Tan SL. 2006. HCV NS5A: a multifunctional regulator of cellular pathways and virus replication, p 267-229. In Tan SL (ed), Hepatitis C virus: genomes and molecular biology. Horizon Bioscience, Norfolk, United Kingdom.
8. Gao M, Nettles RE, Belema M, Snyder LB, Nguyen VN, Fridell RA, Serrano-Wu MH, Langley DR, Sun JH, O'Boyle DR, Jr, Lemm JA, Wang C, Knipe JO, Chien C, Colonno RJ, Grasela DM, Meanwell NA, Hamann LG. 2010. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Natur. 465:96-100. http://dx.doi.org/10.1038/nature08960.
9. Yang PL, Gao M, Lin K, Liu Q, Villareal VA. 2011. Anti-HCV drugs in the pipeline. Curr. Opin. Virol. 1:607-616. http://dx.doi.org/10.1016/j.coviro.2011. 10.019.
10. Lawitz EJ, Gruener D, Hill JM, Marbury T, Moorehead L, Mathias A, Cheng G, Link JO, Wong KA, Mo H, McHutchison JG, Brainard DM. 2012. A phase 1, randomized, placebo-controlled, 3-day, dose-ranging study of GS-5885, an NS5A inhibitor, in patients with genotype 1 hepatitis C. J. Hepatol. 57:24-31. http://dx.doi.org/10.1016/j.jhep.2011.12.029.
11. Merck and Co., Inc. 2007. Isentress (raltegravir) package insert. Merck Sharpe & Dohme, Whitehouse Station, NJ. http://www.merck.com/product/usa/pi- circulars/i/isentress/isentress-pi.pdf.
12. Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, Murthy K, Habermann A, Kräusslich HG, Mizokami M, Bartenschlager R, Liang TJ. 2005. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat. Med. 11:791-796. http://dx.doi.org/10.1038/nm1268.
13. Zhong J, Gastaminza P, Cheng G, Kapadia S, Kato T, Burton DR, Wieland SF, Uprichard SL, Wakita T, Chisari FV. 2005. Robust hepatitis C virus infection in vitro. Proc. Natl. Acad. Sci. U. S. A. 102:9294-9299. http://dx.doi.org/10. 1073/pnas.0503596102.
14. Chackerian B, Long EM, Luciw PA, Overbaugh J. 1997. Human immunodeficiency virus type 1 coreceptors participate in postentry stages in the virus replication cycle and function in simian immunodeficiency virus infection. J. Virol. 71:3932-3939.
15. Nakabayashi H, Taketa K, Miyano K, Yamane T, Sato J. 1982. Growth of human hepatoma cell lines with differentiated functions in chemically defined medium. Cancer Res. 42:3858-3863.
16. Zhu Q, Guo JT, Seeger C. 2003. Replication of hepatitis C virus subgenomes in nonhepatic epithelial and mouse hepatoma cells. J. Virol. 77:9204-9210. http://dx.doi.org/10.1128/JVI.77.17.9204-9210.2003.
17. Buckwold VE, Wilson RJH, Nalca A, Beer BB, Voss TG, Turpin JA, Buckheit RW, III, Wei J, Wenzel-Mathers M, Walton EV, Smith RJ, Pannansch M, Ward P, Wells J, Chuvala L, Sloane S, Paulman R, Russell J, Hartman T, Ptak R. 2004. Antiviral activity of hop constituents against a series of DNA and RNA viruses. Antiviral Res. 61:57-62. http://dx.doi.org/10.1016/S0166-3542(03)00155-4.
18. Prichard MN, Prichard LE, Shipman C, Jr. 1993. Strategic design and three-dimensional analysis of antiviral drug combinations. Antimicrob. Agents Chemother. 37:540-545. http://dx.doi.org/10.1128/AAC.37.3.540.
19. Delaney WE, IV, Yang H, Miller MD, Gibbs CS, Xiong S. 2004. Combinations of adefovir with nucleoside analogs produce additive antiviral effects against hepatitis B virus in vitro. Antimicrob. Agents Chemother. 48:3702-3710. http://dx.doi.org/10.1128/AAC.48.10.3702-3710.2004.
20. Dressler V, Müller G, Sühnel J. 1999. CombiTool-a new computer program for analyzing combination experiments with biologically active agents. Comput. Biomed. Res. 32:145-160. http://dx.doi.org/10.1006/cbmr.1999.1509.
21. Feng JY, Ly JK, Myrick F, Goodman D, White KL, Svarovskaia ES, Borroto-Esoda K, Miller MD. 2009. The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study. Retrovirolog. 6:44-59. http://dx.doi.org/10.1186/ 1742-4690-6-44.
22. Chou TC, Talalay P. 1984. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme Regul. 22:27-55. http://dx.doi.org/10.1016/0065-2571(84)90007-4.
23. AbbVie, Inc. 2000. Kaletra (lopinavir/ritonavir) package insert. AbbVie, Inc., North Chicago, IL. http://www.rxabbvie.com/pdf/kaletratabpi.pdf.
24. Bristol-Myers Squibb Company. 1998. Sustiva (efavirenz) package insert. Bristol-Myers Squibb Company, Princeton, NJ. http://packageinserts.bms.com/pi/ pi-sustiva.pdf.
25. Gilead Sciences, Inc. 2001. Viread (tenofovir) package insert. Gilead Sciences, Inc., Foster City, CA. http://www.gilead.com/+/media/Files/pdfs/ medicines/liver-disease/viread/viread-pi.pdf.
26. GlaxoSmithKline. 1995. Epivir-HBV (lamivudine) package insert. Glaxo-SmithKline, Research Triangle Park, NC. http://us.gsk.com/products/assets/ us-epivir-hbv.pdf.
27. GlaxoSmithKline. 1987. Retrovir (zidovudine) package insert. Glaxo-SmithKline, Research Triangle Park, NC. http://www.accessdata.fda.gov/ drugsatfda-docs/label/2008/019910s033lbl.pdf.
28. Novartis Pharmaceuticals Corporation. 2006. Tyzeka (telbivudine) package insert. Novartis Pharmaceuticals Corporation, East Hanover, NJ. http://www.pharma.us.novartis.com/cs/www.pharma.us.novartis.com/product/pi/pdf/ tyzeka.pdf.
29. van den Hoff M, Moorman A, Lamers W. 1992. Electroporation in 'intracellular' buffer increases cell survival. Nucleic Acids Res. 20:2902. http://dx.doi.org/10.1093/nar/20.11.2902.
30. Molla A, Vasavanonda S, Kumar G, Sham HL, Johnson M, Grabowski B, Denissen JF, Kohlbrenner W, Plattner JJ, Leonard JM, Norbeck DW, Kempf DJ. 1998. Human serum attenuates the activity of protease inhibitors toward wild-type and mutant human immunodeficiency virus. Virolog. 250:255-262. http://dx.doi.org/ 10.1006/viro.1998.9383.
31. Benet LZ, Hoener BA. 2002. Changes in plasma protein binding have little clinical relevance. Clin. Pharmacol. Ther. 71:115-121. http://dx.doi.org/10. 1067/mcp.2002.121829.
32. Gripon P, Rumin S, Urban S, Le Seyec J, Glaise D, Cannie I, Guyomard C, Lucas J, Trepo C, Guguen-Guillouzo C. 2002. Infection of a human hepatoma cell line by hepatitis B virus. Proc. Natl. Acad. Sci. U. S. A. 99:15655-15660. http://dx.doi.org/10.1073/pnas.232137699.
33. Jossé RM, Aninat C, Glaise D, Dumont J, Fessard V, Morel F, Poul JM, Guguen-Guillouza C, Guillouza A. 2008. Long-term functional stability of human HepaRG hepatocytes and use for chronic toxicity and genotoxicity studies. Drug Metab. Dispos. 36:1111-1118. http://dx.doi.org/10.1124/dmd.107.019901.
34. Bort R, Ponsoda X, Jover R, Gómez-Lechón MJ, Castell JV. 1998. Diclofenac toxicity to hepatocytes: a role for drug metabolism in cell toxicity. J. Pharmacol. Exp. Ther. 288:65-72.
35. Nettles RE, Gao M, Bifano M, Chung E, Persson A, Marbury TC, Goldwater R, DeMicco MP, Rodriguez-Torres M, Vutikullird A, Fuentes E, Lawitz E, Lopez-Talavera JC, Grasela DM. 2011. Multiple ascending dose study of BMS-790052, a nonstructural protein 5A replication complex inhibitor, in patients infected with hepatitis C virus genotype 1. Hepatolog. 54:1956-1965. http://dx.doi.org/10.1002/hep.24609.
36. Wang C, Sun JH, O'Boyle DR, Jr, Nower P, Valera L, Roberts S, Fridell RA, Gao M. 2013. Persistence of resistant variants in hepatitis C virusinfected patients treated with the NS5A replication complex inhibitor daclatasvir. Antimicrob. Agents Chemother. 57:2054-2065. http://dx.doi.org/10.1128/AAC.02494- 12.
37. Fridell R, Qiu D, Wang C, Valera L, Gao M. 2010. Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system. Antimicrob. Agents Chemother. 54:3641-3650. http://dx.doi.org/10.1128/AAC.00556- 10.
38. Fridell RA, Wang C, Sun JH, O'Boyle DR, Jr, Nower P, Valera L, Qiu D, Roberts S, Huang X, Kienzle B, Bifano M, Nettles RE, Gao M. 2011. Genotypic and phenotypic analysis of variants resistant to hepatitisCvirus nonstructural protein 5A replication complex inhibitor BMS-790052 in humans: in vitro and in vivo correlations. Hepatolog. 54:1924-1935. http://dx.doi.org/10.1002/hep.24594.
39. Lin HM, Wang JC, Hu HS, Wu PS, Yang CC, Wu CP, Pu SY, Hsu TA, Jiaang WT, Chao YS, Chern JH, Yeh TK, Yueh A. 2011. Resistance analysis and characterization of a thiazole analogue, BP008, as a potent hepatitis C virus NS5A inhibitor. Antimicrob. Agents Chemother. 56:44-
40. http://dx.doi.org/10.1128/AAC.00599-11.
41. Lin HM, Wang JC, Hu HS, Wu PS, Wang WH, Wu SY, Yang CC, Yeh TK, Hsu TA, Jiaang WT, Chao YS, Chern JH, Yueh A. 2012. Resistance studies of a dithiazol analogue, DBPR110, as a potential hepatitis C virus NS5A inhibitor in replicon systems. Antimicrob. Agents Chemother. 57:723-733. http://dx.doi.org/10.1128/ AAC.01403-12.
42. Vince B, Hill JM, Lawitz EJ, O'Riordan W, Webster LR, Gruener DM, Mofsen RS, Murillo A, Donovan E, Chen J, McCarville JF, Sullivan-Bólyai JZ, Mayers D, Zhou XJ. 2014. A randomized, double-blind, multiple-dose study of the pan-genotypic NS5A inhibitor samatasvir in patients infected with hepatitis C virus genotype 1, 2, 3 or 4. J. Hepatol. 60:920-927. http://dx.doi.org/10.1016/ j.jhep.2014.01.003.
43. Liu R, Kong R, Mann P, Ingravallo P, Zhai Y, Xia E, Meinke P, Olsen D, Ludmerer S, Kozlowski J, Coburn C. 2012. In vitro resistance analysis of HCVNS5Ainhibitor: MK-8742 demonstrates increased potency against clinical resistance variants and higher resistance profile. J. Hepatol. 56(Suppl 2):S334-S335. http://dx.doi.org/10.1016/S0168-8278(12)60870-8.
44. Lallos LB, Bilello JP, Soubasakos MA, Gillum J, La Colla M, Serra I, Luizzi M, McCarville J, Seifer M, Good SS, Larsson M, Selden J, Parsy C, Surleraux D, Standring DN. 2009. Preclinical profiles of IDX136 and IDX316, two novel macrocyclic HCV protease inhibitors. J. Hepatol. 50(Suppl 1):S132. http://dx.doi.org/10.1016/S0168-8278(09)60346-9.
45. Cretton-Scott E, Perigaud C, Peyrottes S, Licklider L, Camire M, Larsson M, La Colla M, Hildebrand E, Lallos LB, Bilello JP, McCarville J, Seifer M, Liuzzi M, Pierra C, Badaroux E, Gosselin G, Surleraux D, Standring DN. 2008. In vitro antiviral activity and pharmacology of IDX184, a novel and potent inhibitor of HCV replication. J. Hepatol. 48(Suppl 2):S220. http://dx.doi.org/ 10.1016/S0168-8278(08)60590-5.
46. Nicolas O, Boivin I, St-Denis C, Bedard J. 2008. Genotypic analysis of HCV NS5B variants selected from patients treated with VCH-759. J. Hepatol. 48(Suppl 2):S317. http://dx.doi.org/10.1016/S0168-8278(08)60846-6.
47. Cheng G, Peng B, Corsa A, Yu M, Nash M, Lee YJ, Xu Y, Kirschberg T, Tian Y, Taylor J, Link J, Delaney W, IV. 2012. Antiviral activity and resistance profile of the novel HCV NS5A inhibitor GS-5885. J. Hepatol. 56(Suppl 2):S464. http://dx.doi.org/10.1016/S0168-8278(12)61184-2.
48. Wang C, Huang H, Valera L, Sun JH, O'Boyle DR, Jr, Nower PT, Jia L, Qiu D, Huang X, Altaf A, Gao M, Fridell RA. 2012. Hepatitis C virus RNA elimination and development of resistance in replicon cells treated with BMS-790052. Antimicrob. Agents Chemother. 56:1350-1358. http://dx.doi.org/10.1128/AAC.05977- 11.
49. McCarville J, Seifer M, Standring D, Mayers D. 2013. Treatmentemergent variants following 3 days of monotherapy with IDX719, a potent, pan-genotypic NS5A inhibitor, in subjects infected with HCV genotypes 1-4. J. Hepatol. 58(Suppl 1):S491-S492. http://dx.doi.org/10.1016/S0168-8278(13)61210-6.