Mechanistic characterization and molecular modeling of hepatitis B virus polymerase resistance to entecavir

PLoS ONE

Volumn 5, Issue 2, 2010, Pages

  Walsh, Ann W ^a   Langley, David R ^a   Colonno, Richard J ^a,b   Tenney, Daniel J ^a  

^a BRISTOL MYERS SQUIBB   (United States)

^b Presidio Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENTECAVIR; LAMIVUDINE; POLYMERASE; RNA DIRECTED DNA POLYMERASE; UNCLASSIFIED DRUG; VIRUS ENZYME; ANTIVIRUS AGENT; DRUG DERIVATIVE; GUANINE; GUANOSINE TRIPHOSPHATE; VIRUS PROTEIN;

ARTICLE; CELL CULTURE; ENZYME ACTIVITY; HEPATITIS B VIRUS; HYDROGEN BOND; IN VITRO STUDY; NONHUMAN; PHENOTYPE; VIRUS REPLICATION; VIRUS RESISTANCE; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANTIVIRAL RESISTANCE; BINDING SITE; CELL STRAIN HEPG2; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECT; ENZYME SPECIFICITY; ENZYMOLOGY; GENETICS; HUMAN; KINETICS; METABOLISM; PROTEIN BINDING; PROTEIN TERTIARY STRUCTURE;

HEPATITIS B VIRUS;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANTIVIRAL AGENTS; BINDING SITES; DRUG RESISTANCE, VIRAL; GUANINE; GUANOSINE TRIPHOSPHATE; HEP G2 CELLS; HEPATITIS B VIRUS; HUMANS; HYDROGEN BONDING; KINETICS; LAMIVUDINE; MODELS, MOLECULAR; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; RNA-DIRECTED DNA POLYMERASE; SUBSTRATE SPECIFICITY; VIRAL PROTEINS; VIRUS REPLICATION;

EID: 77949454516     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0009195     Document Type: Article

References (59)

1. Shepard CW, Simard EP, Finelli L, Fiore AE, Bell BP (2006) Hepatitis B Virus Infection: Epidemiology and Vaccination. Epidemiol Rev 28: 112-125.
2. Lok A, McMahon BJ (2007) Chronic hepatitis B. Hepatology 45: 507-539.
3. Langley DR, Walsh AW, Baldick CJ, Eggers BJ, Rose RE, et al. (2007) Inhibition of Hepatitis B Virus Polymerase by Entecavir. J Virol 81: 3992-4001.
4. Seifer M, Hamatake RK, Colonno RJ, Standring DN (1998) In Vitro Inhibition of Hepadnavirus Polymerases by the Triphosphates of BMS-200475 and Lobucavir. Antimicrob Agents Chemother 42: 3200-3208.
5. Tenney DJ, Levine SM, Rose RE, Walsh AW, Weinheimer SP, et al. (2004) Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to Lamivudine. Antimicrob Agents Chemother 48: 3498-3507.
6. Tenney D, Rose R, Baldick C, Pokornowski K, Eggers B, et al. (2009) Long-term Monitoring Shows Hepatitis B Virus Resistance to Entecavir in Nucleoside-Naïve Patients is Rare through 5 Years of Therapy. Hepatology 49: 1503-1514.
7. Baldick CJ, Eggers BJ, Fang J, Levine SM, Pokornowski KA, et al. (2008) Hepatitis B virus quasispecies susceptibility to entecavir confirms the relationship between genotypic resistance and patient virologic response. J Hepatol 48: 895-902.
8. Baldick CJ, Tenney DJ, Mazzucco CE, Eggers BJ, Rose RE, et al. (2008) Comprehensive evaluation of hepatitis B virus reverse transcriptase substitutions associated with entecavir resistance. Hepatology 47: 1473-1482.
9. Levine S, Hernandez D, Yamanaka G, Zhang S, Rose R, et al. (2002) Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro. Antimicrob Agents Chemother 46: 2525-2532.
10. Tenney DJ, Rose RE, Baldick CJ, Levine SM, Pokornowski KA, et al. (2007) Two-Year Assessment of Entecavir Resistance in Lamivudine-Refractory Hepatitis B Virus Patients Reveals Different Clinical Outcomes Depending on the Resistance Substitutions Present. Antimicrob Agents Chemother 51: 902-911.
11. Brunelle MN, Lucifora J, Neyts J, Villet S, Holy A, et al. (2007) In Vitro Activity of 2,4-Diamino-6-[2-(Phosphonomethoxy)Ethoxy]-Pyrimidine against Multidrug-Resistant Hepatitis B Virus Mutants. Antimicrob Agents Chemother 51: 2240-2243.
12. Melegari M, Scaglioni PP, Wands JR (1998) Hepatitis B virus mutants associated with 3TC and famciclovir administration are replication defective. Hepatology 27: 628-633.
13. Ling R, Harrison TJ (1999) Functional analysis of mutations conferring lamivudine resistance on hepatitis B virus. J Gen Virol 80 (Pt 3): 601-606.
14. Ono-Nita SK, Kato N, Shiratori Y, Masaki T, Lan KH, et al. (1999) YMDD motif in hepatitis B virus DNA polymerase influences on replication and lamivudine resistance: A study by in vitro full-length viral DNA transfection. Hepatology 29: 939-945.
15. Urban S, Fischer KP, Tyrrell DL (2001) Efficient pyrophosphorolysis by a hepatitis B virus polymerase may be a primer-unblocking mechanism. Proc Natl Acad Sci U S A 98: 4984-4989.
16. Boyer PL, Julias JG, Marquez VE, Hughes SH (2005) Fixed conformation nucleoside analogs effectively inhibit excision-proficient HIV-1 reverse transcriptases. J Mol Biol 345: 441-450.
17. Tchesnokov EP, Obikhod A, Schinazi RF, Gotte M (2008) Delayed chain termination protects the anti-hepatitis B virus drug entecavir from excision by HIV-1 reverse transcriptase. J Biol Chem 283: 34218-34228.
18. Das K, Xiong X, Yang H, Westland CE, Gibbs CS, et al. (2001) Molecular modeling and biochemical characterization reveal the mechanism of hepatitis B virus polymerase resistance to lamivudine (3TC) and emtricitabine (FTC). J Virol 75: 4771-4779.
19. Seifer M, Hamatake R, Bifano M, Standring DN (1998) Generation of replication-competent hepatitis B virus nucleocapsids in insect cells. J Virol 72: 2765-2776.
20. Allen MI, Deslauriers M, Andrews CW, Tipples GA, Walters KA, et al. (1998) Identification and characterization of mutations in hepatitis B virus resistant to lamivudine. Lamivudine Clinical Investigation Group. Hepatology 27: 1670-1677.
21. Tipples GA, Ma MM, Fischer KP, Bain VG, Kneteman NM, et al. (1996) Mutation in HBV RNA-dependent DNA polymerase confers resistance to lamivudine in vivo. Hepatology 24: 714-717.
22. Ling R, Mutimer D, Ahmed M, Boxall EH, Elias E, et al. (1996) Selection of mutations in the hepatitis B virus polymerase during therapy of transplant recipients with lamivudine. Hepatology 24: 711-713.
23. Chin R, Shaw T, Torresi J, Sozzi V, Trautwein C, et al. (2001) In vitro susceptibilities of wild-type or drug-resistant hepatitis B virus to (-)-beta-D-2,6-diaminopurine dioxolane and 2′-fluoro-5-methyl-beta-L- arabinofuranosyluracil. Antimicrob Agents Chemother 45: 2495-2501.
24. Wilson JE, Aulabaugh A, Caligan B, McPherson S, Wakefield JK, et al. (1996) Human immunodeficiency virus type-1 reverse transcriptase. Contribution of Met-184 to binding of nucleoside 5′-triphosphate. J Biol Chem 271: 13656-13662.
25. Schinazi RF, Lloyd RM Jr, Nguyen MH, Cannon DL, McMillan A, et al. (1993) Characterization of human immunodeficiency viruses resistant to oxathiolanecytosine nucleosides. Antimicrob Agents Chemother 37: 875-881.
26. Boucher CA, Cammack N, Schipper P, Schuurman R, Rouse P, et al. (1993) High-level resistance to (-) enantiomeric 2′-deoxy-3′-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 37: 2231-2234.
27. Tisdale M, Kemp SD, Parry NR, Larder BA (1993) Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3′-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. Proc Natl Acad Sci U S A 90: 5653-5656.
28. Fung SK, Andreone P, Han SH, Rajender Reddy K, Regev A, et al. (2005) Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation. J Hepatol 43: 937-943.
29. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, et al. (2005) Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med 352: 2673-2681.
30. Yadav V, Chu CK (2004) Molecular mechanisms of adefovir sensitivity and resistance in HBV polymerase mutants: a molecular dynamics study. Bioorg Med Chem Lett 14: 4313-4317.
31. Bartholomeusz A, Tehan BG, Chalmers DK (2004) Comparisons of the HBV and HIV polymerase, and antiviral resistance mutations. Antivir Ther 9: 149-160.
32. Tatti KM, Korba BE, Stang HL, Peek S, Gerin JL, et al. (2002) Mutations in the conserved woodchuck hepatitis virus polymerase FLLA and YMDD regions conferring resistance to lamivudine. Antiviral Res 55: 141-150.
33. Villet S, Pichoud C, Billioud G, Barraud L, Durantel S, et al. (2008) Impact of hepatitis B virus rtA181V/T mutants on hepatitis B treatment failure. Journal of Hepatology 48: 747-755.
34. Gaillard RK, Barnard J, Lopez V, Hodges P, Bourne E, et al. (2002) Kinetic analysis of wild-type and YMDD mutant hepatitis B virus polymerases and effects of deoxyribonucleotide concentrations on polymerase activity. Antimicrob Agents Chemother 46: 1005-1013.
35. Sarafianos SG, Marchand B, Das K, Himmel DM, Parniak MA, et al. (2009) Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition. J Mol Biol 385: 693-713.
36. Domaoal RA, McMahon M, Thio CL, Bailey CM, Tirado-Rives J, et al. (2008) Pre-steady-state kinetic studies establish entecavir 5′-triphosphate as a substrate for HIV-1 reverse transcriptase. J Biol Chem 283: 5452-5459.
37. Boyer PL, Julias JG, Ambrose Z, Siddiqui MA, Marquez VE, et al. (2007) The nucleoside analogs 4'C-methyl thymidine and 4'C-ethyl thymidine block DNA synthesis by wild-type HIV-1 RT and excision proficient NRTI resistant RT variants. J Mol Biol 371: 873-882.
38. Lin PF, Nowicka-Sans B, Terry B, Zhang S, Wang C, et al. (2008) Entecavir exhibits inhibitory activity against human immunodeficiency virus under conditions of reduced viral challenge. Antimicrob Agents Chemother 52: 1759-1767.
39. Innaimo SF, Seifer M, Bisacchi GS, Standring DN, Zahler R, et al. (1997) Identification of BMS-200475 as a potent and selective inhibitor of hepatitis B virus. Antimicrob Agents Chemother 41: 1444-1448.
40. Colonno RJ, Rose R, Baldick CJ, Levine S, Pokornowski K, et al. (2006) Entecavir resistance is rare in nucleoside naive patients with hepatitis B. Hepatology 44: 1656-1665.
41. Fallows DA, Goff SP (1995) Mutations in the epsilon sequences of human hepatitis B virus affect both RNA encapsidation and reverse transcription. J Virol 69: 3067-3073.
42. Kaplan PM, Ford EC, Purcell RH, Gerin JL (1976) Demonstration of subpopulations of Dane particles. J Virol 17: 885-893.
43. Oberg B (1989) Antiviral effects of phosphonoformate (PFA, foscarnet sodium). Pharmacol Ther 40: 213-285.
44. Nordenfelt E, Oberg B, Helgstrand E, Miller E (1980) Inhibition of hepatitis B Dane particle DNA polymerase activity by pyrophosphate analogs. Acta Pathol Microbiol Scand B 88: 169-175.
45. Hess G, Arnold W, Meyer zum Buschenfelde KH (1980) Inhibition of hepatitis-B-virus DNA polymerase by phosphonoformate: studies on its mode of action. J Med Virol 5: 309-316.
46. Lanford RE, Notvall L, Beames B (1995) Nucleotide priming and reverse transcriptase activity of hepatitis B virus polymerase expressed in insect cells. J Virol 69: 4431-4439.
47. Favre D (2008) Reverse transcriptase activity of hepatitis B virus polymerase in eukaryotic cell extracts in vitro. Altex 25: 197-211.
48. McMillan JS, Shaw T, Angus PW, Locarnini SA (1995) Effect of immunosuppressive and antiviral agents on hepatitis B virus replication in vitro. Hepatology 22: 36-43.
49. Cheng Y, Prusoff WH (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22: 3099-3108.
50. Huang H, Chopra R, Verdine GL, Harrison SC (1998) Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 282: 1669-1675.
51. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. Journal of Computational Chemistry 4: 187-217.
52. Momany FA, Rone R (1992) Validation of the general purpose QUANTA ®3.2/CHARMm® force field. Journal of Computational Chemistry 13: 888-900.
53. MacKerell AD, Bashford D, Bellott M, Dunbrack RL, Evanseck JD, et al. (1998) All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins. J Phys Chem B 102: 3586-3616.
54. Foloppe N, MacKerell AD (2000) All-atom empirical force field for nucleic acids: I. Parameter optimization based on small molecule and condensed phase macromolecular target data. Journal of Computational Chemistry 21: 86-104.
55. Nilsson L, Karplus M (1986) Empirical energy functions for energy minimization and dynamics of nucleic acids. Journal of Computational Chemistry 7: 591-616.
56. Tidor B, Irikura KK, Brooks BR, Karplus M (1983) Dynamics of DNA oligomers. J Biomol Struct Dyn 1: 231-252.
57. Dominy BN, Brooks CL (1999) Development of a Generalized Born Model Parametrization for Proteins and Nucleic Acids. J Phys Chem B 103: 3765-3773.
58. Verlet L (1967) Computer "Experiments" on Classical Fluids. I. Thermodynamical Properties of Lennard-Jones Molecules. Physical Review 159: 98 - 103.
59. Ryckaert J-P, Ciccotti G, Berendsen HJC (1977) Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. Journal of Computational Physics 23: 327-341.