Resensitizing daclatasvir-resistant hepatitis C variants by allosteric modulation of NS5A

Nature

Volumn 527, Issue 7577, 2015, Pages 245-248

  Sun, Jin Hua ^a   O'Boyle, Donald R ^a   Fridell, Robert A ^a   Langley, David R ^a   Wang, Chunfu ^a   Roberts, Susan B ^a   Nower, Peter ^a   Johnson, Benjamin M ^a   Moulin, Frederic ^a   Nophsker, Michelle J ^a   Wang, Ying Kai ^a   Liu, Mengping ^a   Rigat, Karen ^a   Tu, Yong ^a   Hewawasam, Piyasena ^a   Kadow, John ^a   Meanwell, Nicholas A ^a   Cockett, Mark ^a   Lemm, Julie A ^a   Kramer, Melissa ^a   Belema, Makonen ^a   Gao, Min ^a   more..

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BMS 393; DIMER; NONSTRUCTURAL PROTEIN 5A; NONSTRUCTURAL PROTEIN 5A INHIBITOR; SYN 395; UNCLASSIFIED DRUG; ANTIVIRUS AGENT; BIPHENYL DERIVATIVE; BMS-790052; IMIDAZOLE DERIVATIVE; NS-5 PROTEIN, HEPATITIS C VIRUS; SYN-395; VIRUS PROTEIN;

ANTIMICROBIAL ACTIVITY; DISEASE RESISTANCE; HEPATITIS; INHIBITION; INHIBITOR; PROTEIN; RODENT; VIRAL DISEASE;

ALLOSTERISM; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIVIRAL ACTIVITY; ARTICLE; COMBINATION CHEMOTHERAPY; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DIASTEREOISOMER; DRUG POTENCY; DRUG POTENTIATION; DRUG TOLERABILITY; EC50; GENOTYPE; HEPATITIS C; HUMAN; HUMAN CELL; IN VIVO STUDY; MALE; MOUSE; MOUSE MODEL; NONHUMAN; PRIORITY JOURNAL; SINGLE DRUG DOSE; VIRUS INHIBITION; VIRUS REPLICATION; ANIMAL; ANTIVIRAL RESISTANCE; CELL LINE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG COMBINATION; DRUG EFFECTS; GENETICS; HEPACIVIRUS; LIVER CELL; METABOLISM; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION; PROTEIN QUATERNARY STRUCTURE; REPRODUCIBILITY; TRANSPLANTATION; VIROLOGY;

DROSOPHILA C VIRUS; HEPATITIS C VIRUS;

ALLOSTERIC REGULATION; ANIMALS; ANTIVIRAL AGENTS; BIPHENYL COMPOUNDS; CELL LINE; DRUG RESISTANCE, VIRAL; DRUG SYNERGISM; DRUG THERAPY, COMBINATION; HEPACIVIRUS; HEPATITIS C; HEPATOCYTES; HUMANS; IMIDAZOLES; MICE; MODELS, MOLECULAR; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, QUATERNARY; REPRODUCIBILITY OF RESULTS; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION;

EID: 84946909697     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature15711     Document Type: Article

References (28)

1. Mohd Hanafiah, K., Groeger, J., Flaxman, A. D. & Wiersma, S. T. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology 57, 1333-1342 (2013).
2. Shepard, C. W., Finelli, L. & Alter, M. J. Global epidemiology of hepatitis C virus infection. Lancet Infect. Dis. 5, 558-567 (2005).
3. Pawlotsky, J. M. NS5A inhibitors in the treatment of hepatitis C. J. Hepatol. 59, 375-382 (2013).
4. Guedj, J. et al. Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life. Proc. Natl Acad. Sci. USA 110, 3991-3996 (2013).
5. Macdonald, A. & Harris, M. Hepatitis C virus NS5A: tales of a promiscuous protein. J. Gen. Virol. 85, 2485-2502 (2004).
6. He, Y., Staschke, K. A. & Tan, S.-L. in Hepatitis C Viruses Genomes and Molecular Biology (ed. Tan, S.-L.) Ch. 9, 267-291 (Horizon Bioscience, 2006).
7. Tellinghuisen, T. L., Marcotrigiano, J. & Rice, C. M. Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase. Nature 435, 374-379 (2005).
8. Love, R. A., Brodsky, O., Hickey, M. J., Wells, P. A. & Cronin, C. N. Crystal structure of a novel dimeric form of NS5A domain I protein from hepatitis C virus. J. Virol. 83, 4395-4403 (2009).
9. Lambert, S. M. et al. The crystal structure of NS5A domain 1 from genotype 1a reveals new clues to the mechanism of action for dimeric HCV inhibitors. Protein Sci. 23, 723-734 (2014).
10. Gao, M. et al. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature 465, 96-100 (2010).
11. Quinkert, D., Bartenschlager, R. & Lohmann, V. Quantitative analysis of the hepatitis C virus replication complex. J. Virol. 79, 13594-13605 (2005).
12. Pietschmann, T., Lohmann, V., Rutter, G., Kurpanek, K. & Bartenschlager, R. Characterization of cell lines carrying self-replicating hepatitis C virus RNAs. J. Virol. 75, 1252-1264 (2001).
13. O'Boyle, D. R. II et al. Characterizations of HCV NS5A replication complex inhibitors. Virology 444, 343-354 (2013).
14. Fridell, R. A., Qiu, D., Wang, C., Valera, L. & Gao, M. Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system. Antimicrob. Agents Chemother. 54, 3641-3650 (2010).
15. Pelosi, L. A., Voss, S., Liu, M., Gao, M. & Lemm, J. A. Effect on hepatitis C virus replication of combinations of direct-acting antivirals, including NS5A inhibitor daclatasvir. Antimicrob. Agents Chemother. 56, 5230-5239 (2012).
16. Nettles, R. E. et al. BMS-824393 is a potent HCV NS5A inhibitor with substantial antiviral activity when given as monotherapy in subjects with chronic G1 HCV infection. 61th Ann. Meeting AASLD (2010).
17. Sandgren, E. P. et al. Complete hepatic regeneration after somatic deletion of an albumin-plasminogen activator transgene. Cell 66, 245-256 (1991).
18. Hernandez, D., Zhou, N., Ueland, J., Monikowski, A. & McPhee, F. Natural prevalence of NS5A polymorphisms in subjects infected with hepatitis C virus genotype 3 and their effects on the antiviral activity of NS5A inhibitors. J. Clin. Virol. 57, 13-18 (2013).
19. McCarville, J. F., Seifer, M., Standring, D. N., Mayers, D. L. & IDX-06A-001 Investigator Team. Treatment-emergent 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 (2013).
20. Everson, G. T. et al. Phase 2b study of the interferon-free and ribavirin-free combination of daclatasvir, asunaprevir, and BMS-791325 for 12 weeks in treatment-naive patients with chronic HCV genotype 1 infection. 64th Ann. Meeting AASLD (2013).
21. Penin, F. et al. Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A. J. Biol. Chem. 279, 40835-40843 (2004).
22. Pack, S. K. et al. Hepatitis C virus inhibitors. US patent 9,006,455 B2 (2015).
23. St. Laurent, D. R. et al. HCV NS5A replication complex inhibitors. Part 4. Optimization for genotype 1a replicon inhibitory activity. J. Med. Chem. 57, 1976-1994 (2014).
24. Seebach, D., Naef, R. & Calderari, G. α-Alkylation of α-heterosubstituted carboxylic acids without racemization. Tetrahedron 40, 1313-1324 (1984).
25. Nagase, R., Oguni, Y., Misaki, T. & Tanabe, Y. Practical and robust method for the preparation of Seebach and Frater's chiral template, cis-2-substituted 5-methyl (or phenyl)-1,3-dioxolan-4-ones. Synthesis 22, 3915-3917 (2006).
26. Reddy, L. R., Gupta, A. P. & Liu, Y. Asymmetric synthesis of α-amino acids by reduction of N-tert-butanesulfinyl ketimine esters. J. Org. Chem. 76, 3409-3415 (2011).
27. Link, J. O. et al. Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection. J. Med. Chem. 57, 2033-2046 (2014).
28. Baldick, C. J. et al. A novel small molecule inhibitor of hepatitis C virus entry. PLoS Pathog. 6, e1001086 (2010).