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Drug discovery and development of antiviral agents for the treatment of chronic hepatitis B virus infection

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Book cover Antiviral Agents

Part of the book series: Progress in Drug Research ((PDR,volume 500))

Summary

A safe and effective vaccine for hepatitis B virus (HBV) has been available for nearly twenty years and currently campaigns to provide universal vaccination in developing countries are underway. Nevertheless, chronic HBV infection remains a leading cause of chronic hepatitis worldwide and there is a strong need for safe and effective antiviral therapies. Attempts to identify and develop antiviral agents to treat chronic HBV infection remains focused on nucleoside analogs such as 3TC (lamivudine), adefovir dipivoxil, (bis-POM PMEA), and others. However, advances in our understanding of the molecular biology of HBV and the development of new assays for HBV polymerase activity, such as the reconstitution of active HBV polymerase in vitro, should facilitate large screening efforts for non-nucleoside reverse transcriptase inhibitors. Recent advances have furthered our understanding of clinical resistance to lamivudine, have provided new approaches to treatment, and have offered new perspectives on the major challenges to the identification and development of antiviral agents for chronic HBV infection. Here, in an update to our previous review article that appeared in this series [59a], we focus on recent advances that have occurred in the areas of virus structure and replication, in vitro viral polymerase assays, cell culture systems, and animal models.

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Abbreviations

ACV:

9(2-hydroxyethoxymethyl)guanine (acyclovir)

ACV-MP:

5′-monophosphate of acyclovir

ACV-TP:

5′-triphosphate of acyclovir

ara-A:

9-ß-D-arabinofuranosyladenine

ara-AMP:

5′-monophosphate of 9-ß-D-arabinofuranosyladenine

AZT:

3′-azido-3′-deoxythymidine; bis-POM PMEA,bis[(pivaloyloxy)methyl] derivative of PMEA (GS-840)

CCC DNA:

covalently closed circular DNA

CC50 :

cytotoxic concentration, 50%

CDG:

carbocyclic analog of 2′deoxyguanosine

CMV:

cytomegalovirus infection

CTL:

cytotoxic Tlymphocyte

DAPD:

(-)-ß-D-2,6-diaminopurine dioxolane

ddA:

2′,3′-dideoxyadenine

ddC:

2′,3′-dideoxycytidine

ddCMP:

5′-monophosphate of ddC

ddI:

-2′,3′dideoxyinosine

d4C:

deoxy-2′,3′-didehydrocytidine

d4T:

3′deoxy-2′,3′-didehydrothymidine

dGTP:

5′-triphosphate of deoxyguanosine

DHBV:

duck hepatitis B virus

dTTP:

5′-triphosphate of thymidine

DXG:

dioxolane guanosine

EC50 :

effective concentration, 50%

EC90 :

effective concentration, 90%

FEAU:

2′-deoxy-2′-fluoro-1-ß-D-arabinofuranosy1-5-ethyluracil

FIAC:

2′-deoxy-2′-fluoro-1-ß-D-arabinofuranosy1-5-iodocytosine

FIAU:

2′deoxy-2′fluoro-1-ß-D-arabinofuranosy1-5-iodouracil (fialuridine)

FIAU-TP:

5′-triphosphate of FIAU

FLG:

2′,3′-dideoxy-3′-fluoroguanosine

FLT:

3′-deoxy-3′-fluorothymidine

FMAU:

2′-deoxy-2′-fluoro-1-ß-D-arabinofuranosy1-5-methyluracil

FTC:

(-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine

GCV:

ganciclovir (9-(1,3-dihydroxy-2-propoxymethyl)guanine)

GSHV:

ground squirrel hepatitis virus

HBcAg:

hepatitis B virus c (or core) antigen

HBeAg:

hepatitis B virus e (or envelope) antigen

HBsAg:

hepatitis B virus s (or surface) antigen

HBV:

hepatitis B virus

HIV:

human immunodeficiency virus

HPMPC:

(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (cidofovir)

IC50 :

inhibitory concentration, 50%

IFN:

interferon

L-FMAU:

the L enantiomer of FMAU

L-HSA:

lactosaminated human serum albumin

NAC:

N-acetyl-L-cysteine

NBDNJ:

N-butyldeoxynojirimycin

OLT:

orthotopic liver transplantation

PAA:

phosphonoacetic acid

PFA:

phosphonoformic acid (foscarnet)

PMEA:

9-2-phosphonylmethoxyethyladenine

RNP:

ribonucleoprotein

SI:

selective index

3TC:

(2R, 5S) 1[2-(hydroxymethyl)-1,3-oxathiolane-5-yllcytosine (lamivudine;(-)BCH-189)

WHV:

woodchuck hepatitis virus

References

  1. Abbruzzese, J.L., Schmidt, S., Raber, M.N., Levy, J.K., Castellanos, A.M., Legha, S.S. and Kroakoff I.H.: Invest. New Drugs 7, 195–201 (1989).

    Article  PubMed  CAS  Google Scholar 

  2. Acs, G., Sells, M.A., Purcell, R.H., Price, P., Engle, R., Shapiro, M. and Popper, H.: Proc. Natl. Acad. Sci. USA 84, 4641–4644 (1987).

    Article  CAS  Google Scholar 

  3. Aguesse-Germon, S., Liu, S.H., Chevallier, M., Pichoud, C., Jamard, C., Borel, C., Chu, C.K., Trepo, C., Cheng, Y.C. and Zoulim, F.: Antimicrob. Agents Chemother. 42, 369–376 (1998).

    PubMed  CAS  Google Scholar 

  4. Aldrich, C.E., Coates, L., Wu, T.T., Newbold, J., Tennant, B.C., Summers, J., Seeger, C. and Mason, W.S.: Virology 172, 247–252 (1989).

    Article  CAS  Google Scholar 

  5. Alexander, G.J., Fagan, E.A., Hegarty, J.E., Yeo, J., Eddleston, A.L. and Williams, R.: J. Med. Virol. 21, 81–87 (1987).

    Article  PubMed  CAS  Google Scholar 

  6. Allen, M.I., Deslauriers, M., Andrews, C.W., Tipples, G.A., Walters, K.A., Tyrrell, D.L., Brown, N. (for the Lamivudine Clincical Investigation Group) and Condreay, L.D.: Hepatology 27, 1670–1677 (1998).

    Article  CAS  Google Scholar 

  7. Anand, B.S., Yoffe, B. and Young, J.B.: J. Clin. Gastroenterology 22, 144–146 (1996).

    Article  CAS  Google Scholar 

  8. Araki, K., Miyazaki, J., Hino, O., Tornita, N., Chisaka, O., Matsubara, K. and Yamamura, K.: Proc. Natl. Acad. Sci. USA 86, 207–211 (1989).

    Article  CAS  Google Scholar 

  9. Ashwell, G. and Hartford, J.: Annu. Rev. Biochem. 51, 531–534 (1982).

    Article  PubMed  CAS  Google Scholar 

  10. Aye, T.T., Bartholomeuz, A., Shaw, T., Breschkin, A., Groenen, L., Bowden, S., McMillan, J., Angus, P., McCaughan, G.W. and Locarnini, S.: Hepatology 24, 285A (1996).

    Google Scholar 

  11. Aye, T.T., Bartholomeuz, A., Shaw, T., Bowden, S., Breschkin, A., McMillan, J., Angus, P. and Locarnini, S.: J. Hepatology 26, 1148–1153 (1997).

    Article  CAS  Google Scholar 

  12. Bain, V.G., Daniels, H.M., Chanas, A., Alexander, G.J.M. and Williams, R.: J. Med. Virol. 29, 152–155 (1989).

    Article  PubMed  CAS  Google Scholar 

  13. Bain, V.G., Kneteman, N.M., Ma, M.M., Gutfreund, K., Shapiro, J.A., Fischer, K., Tipples, G., Lee, H., Jewell, L.D. and Tyrrell, D.L.: Transplantation 62, 1456–1462 (1996).

    Article  CAS  Google Scholar 

  14. Baltimore, D.: Nature 325, 395–396 (1988).

    Article  Google Scholar 

  15. Balzarini,.J, Kruining, J., Wedgwood, O., Pannecouque, C., Aquaro, S., Perno, C.F., Naesens, L., Witvrouw, M., Heijtink, R., De Clercq, E. and McGuigan, C.: FEBS Lett. 410, 324–328 (1997).

    Google Scholar 

  16. Barditch-Crovo, P., Toole, J., Hendrix, C.W., Cundy, K.C., Ebeling, D., Jaffe, H.S. and Lietman, P.S.: J. Inf. Dis. 176, 406–413 (1997).

    Article  CAS  Google Scholar 

  17. Bartholomeusz, A. and Locarnini, S.: Intl. Antiviral News 5, 123–124 (1997).

    Google Scholar 

  18. Bartholomeusz, A., Groenen, L.C. and Locarnini, S.A.: Intervirology 40, 337–342 (1997).

    Article  CAS  Google Scholar 

  19. Bartholomew, M.M., Jansen, R.W., Jeffers, L.J., Reddy, K.R., Johnson, L.C., Bunzendahl, H., Condreay, L.D., Tzakis, A.G., Schiff, E.R. and Brown, N.A.: Lancet 349, 20–22 (1997).

    Article  CAS  Google Scholar 

  20. Bassendine, M.P., Chadwick, R.G., Salmeron, J., Shipton, U., Thomas, H.C. and Sherlock, S.: Gastroenterology 80, 1016–1022 (1981).

    PubMed  CAS  Google Scholar 

  21. Bean, B.: Clin. Microbiol. Rev. 5, 146–182 (1992).

    CAS  Google Scholar 

  22. Beck, J. and Nassal, M.: Nucleic Acids Res. 23, 4954–4962 (1995).

    Article  PubMed  CAS  Google Scholar 

  23. Benhamou, Y., Katlama, C., Lunel, F., Coutellier, A., Dohin, E., Hamm, N., Tubiana, R., Herson, S., Poynard, T. and Opolom, P.: Ann. Int. Med. 125, 705–712 (1996).

    PubMed  CAS  Google Scholar 

  24. Berk, L., Schalm, S.W. and Heijtink, R.A.: Antiviral Res. 19, 111–118 (1992).

    Article  CAS  Google Scholar 

  25. Berk, L., Schalm, S.W., de Man, R.A., Heijtink, R.A., Berthelot, P., Brechot, C., Boboc, B., Degos et al.: J. Hepatology 14, 305–309 (1992).

    Article  CAS  Google Scholar 

  26. Beterams, G., Bottcher, B. and Nassal, M.: FEBS Lett. 481, 169–176 (2000).

    Article  CAS  Google Scholar 

  27. Bisacchi, G.S., Chao, S.T., Bachard, C., Dads, J.P., Innaimo, S., Jacobs, G.A., Kocy, O., Lapointe, P., Martel, A., Merchant, Z., Slusarchyk, W.A., Sundeen, J.I., Young, M.G., Colonno, R. and Zahler, R.: Bioorg. Med. Chem. Lett. 7, 127–132 (1997).

    Article  CAS  Google Scholar 

  28. Block, T.M., Lu, X., Mehta, A.S., Blumberg, B.S., Tennant, B., Ebling, M., Korba, B., Lansky, D.M., Jacob, G.S. and Dwek, R.A.: Nat. Med. 4, 610–614 (1998).

    Article  PubMed  CAS  Google Scholar 

  29. Block, T.M., Lu, X., Platt, F.M., Foster, G.R., Gerlich, W.H., Blumberg, B.S. and Dwek, R.A.: Proc. Natl. Acad. Sci. USA 91, 2235–2239 (1994).

    Article  CAS  Google Scholar 

  30. Blum, H.E., Zhang, Z.S., Galun, E., von Weizsacker, E, Garner, B., Liang, T.J. and Wands, J.R.: J Virol. 66, 1223–1227 (1992).

    CAS  Google Scholar 

  31. Boker, K.H.W., Ringe, B., Kruger, M., Pichlmayer, R. and Manns, M.P.: Transplantation 57, 1706–1708 (1994).

    PubMed  CAS  Google Scholar 

  32. Boyd, M.R., Bacon, T.H., Sutton, D. and Cole, M.: Antimicrob. Agents Chemother. 31, 1238–1242 (1987).

    Article  PubMed  CAS  Google Scholar 

  33. Brook, M.G., Petrovic, L., McDonald, J.A., Scheuer, P.J. and Thomas, H.C.: J. Hepatol. 8, 218–225 (1989).

    Article  PubMed  CAS  Google Scholar 

  34. Bruss, V. and Ganem, D.: Proc. Natl. Acad. Sci. USA 88, 1059–1063 (1991).

    Article  CAS  Google Scholar 

  35. Bunnell, B.A., Askari, F.K. and Wilson, J.M.: Cell Mol. Genet. 18, 559–569 (1992).

    Article  CAS  Google Scholar 

  36. Burgess, J.B., Baenziger, J.U. and Brown, W.R.: Hepatology 15, 702–706 (1992).

    Article  CAS  Google Scholar 

  37. Catapano, C.V., Perrino, F.W. and Fernandes, D.J.: J. Biol. Chem. 268, 7179–7185 (1993).

    PubMed  CAS  Google Scholar 

  38. Catterall, A.P., Moyle, G.J., Hopes, E.A., Harrison, T.J., Gazzard, B.G. and Murray-Lyon, I.M.: J. Med. Virol. 37, 307–309 (1992).

    Article  PubMed  CAS  Google Scholar 

  39. Cerenzia, M.T., Fiume, L., Venon, W.D.B., Lavezzo, B., Brunetto, M.R., Ponzetto, M., Di Stefano, G., Busi, C., Mattioli, A., Gervasi, G.B., Bonino, F. and Verme, G.: Hepatology 23, 657–661 (1996).

    Article  CAS  Google Scholar 

  40. Chachoua, A., Dieterich, D., Krasinski, K., Greene, J., Laubenstein, L., Wernz, J., Buhles, W. and Koretz, S.: Ann. Int. Med. 107, 133–137 (1987).

    PubMed  CAS  Google Scholar 

  41. Chang,.IM.: Phytotherapy Res. 11, 189–192 (1997).

    Article  CAS  Google Scholar 

  42. Chang, C.M., Jeng, K.S., Hu, C.P., Lo, S.J., Su, T.S., Ting, L.P., Chou, C.K., Han, S.H., Pfaff, E., Salfeld, J., et al.: EMBO J. 6, 675–680 (1987).

    PubMed  CAS  Google Scholar 

  43. Chang, C.N., Doong, S.L., Zhou, J.H., Beach, J.W., Jeong, L.S., Chu, C.K., Tsai, C.H., Cheng, Y.C., Liotta, D. and Schinazi, R.: J. Biol. Chem. 267, 13938–13942 (1992).

    PubMed  CAS  Google Scholar 

  44. Chang, L.J., Pryciak, P., Ganem, D. and Varmus, H.E.: Nature 337, 364–368 (1989).

    Article  CAS  Google Scholar 

  45. Charvet, A.S., Turin, F., Faury, P., Hantz, O., Camplo, M., Mourier, N., Berthillon, P., Graciet, J.C., Chermann, J.C., Trepo, C. and Kraus, J.L.: Antiviral Res. 25, 161–168 (1994).

    Article  CAS  Google Scholar 

  46. Chen, C.H. and Cheng, Y.C.: J. Biol. Chem. 264, 11934–11937 (1989).

    PubMed  CAS  Google Scholar 

  47. Chen, C.H. and Cheng, Y.C.: J. Biol. Chem. 267, 2856–2859 (1992).

    PubMed  CAS  Google Scholar 

  48. Chen, H.C., Chou, C.K., Sun, C.M. and Yeh, S.F.: Antiviral Res. 34, 137–144 (1997).

    Article  CAS  Google Scholar 

  49. Chen, H., Schinazi, R.F., Rajagopalan, P., Gao, Z., Chu, C.K., McClure, H.M. and Boudinot, F,D.: AIDS Res. Hum. Retroviruses 15, 1625–1630 (1999).

    Article  PubMed  CAS  Google Scholar 

  50. Chen, M.S., Van Nostrand, M. and Oshana, S.C.: Anal. Biochem. 156, 300–304 (1986).

    Article  PubMed  CAS  Google Scholar 

  51. Chesnut, R.W., Sette, A., Celis, E., Wentworth, P., Kubo, R.T., Alexander, J., Ishioka, G., Vitiello, A. and Grey, H.M.: Pharmaceutical Biotechnology 6, 847–874 (1995).

    Article  CAS  Google Scholar 

  52. Chiou, J.F. and Cheng, Y.C.: Agents Chemother. 27, 416–418 (1985).

    Article  CAS  Google Scholar 

  53. Chisari, F.V. and Ferrari, C.: Annu. Rev. Immunol. 13, 29–60 (1995).

    Article  PubMed  CAS  Google Scholar 

  54. Chisari, F.V., Ferrari, C. and Mondelli, M.U.: Microbial Pathogenesis 6, 311–325 (1989).

    Article  CAS  Google Scholar 

  55. Cho, G., Park, S.G. and Jung, G.: Biochem. Biophys. Res. Commun. 269, 191–196 (2000a).

    Article  CAS  Google Scholar 

  56. Cho, G., Suh, S.W. and Jung, G.: Biochem. Biophys. Res. Commun. 274, 203–211 (2000b).

    Article  CAS  Google Scholar 

  57. Chou, T.C., Kong, X.B., Fanucchi, M.P., Cheng, Y.C., Takahashi, K., Watanabe, K.A. and Fox, J.J.: Antimicrob Agents Chemother. 31, 1355–1358 (1987).

    Article  CAS  Google Scholar 

  58. Chu, C.K., Boudinot, F.D., Peek, S.F., Hong, J.A., Choi, Y., Korba, B.E., Gerin, J.L., Cote, P.J., Tennant, B.C. and Cheng, Y.C.: Antivir. Ther. 3, 113–121 (1998).

    PubMed  CAS  Google Scholar 

  59. Chu, C.K., Ma, T., Shanmuganathan, K., Wang, C., Xiang, Y., Pai, S.B., Yao, G.Q., Sommadossi, J.P. and Cheng, Y.C.: Antimicrob. Agents Chemother. 39, 979–981 (1995).

    Article  PubMed  CAS  Google Scholar 

  60. Civitico, G.M. and Locarnini, S.A.: Virology 203, 81–89 (1994).

    Article  PubMed  CAS  Google Scholar 

  61. Civitico, G., Shaw, T. and Locarnini, S.: Antimicrob. Agents Chemother. 40, 1180–1185 (1996).

    PubMed  CAS  Google Scholar 

  62. Civitico, G., Wang, Y.Y., Luscombe, C., Bishop, N., Tachedjian, G., Gust, I. and Locarnini, S.: J. Med. Virol. 31, 90–97 (1990).

    Article  PubMed  CAS  Google Scholar 

  63. Coates, J.A., Cammack, N, and Jenkinson, H.J.: Antimicrob. Agents Chemother. 36, 202–205 (1992).

    Article  PubMed  CAS  Google Scholar 

  64. Colacino, J.M.: Antiviral Res. 29, 125–139 (1996).

    Article  PubMed  CAS  Google Scholar 

  65. Colacino, J. and Lopez, C.: Antimicrob. Agents Chemother. 25, 505–508 (1983).

    Article  Google Scholar 

  66. Colacino, J., Brownridge, E., Greenberg, N. and Lopez, C.: Antimicrob. Agents Chemother. 29, 877–892 (1986).

    Article  PubMed  CAS  Google Scholar 

  67. Colacino, J.M., Malcolm, S.K. and Jaskunas, S.R.: Antimicrob. Agents Chemother. 38, 1997–2002 (1994).

    Article  PubMed  CAS  Google Scholar 

  68. Colacino, J.M., Horn, J.W., Horn D,M. and Richardson, F.C.: Tox. In Vitro 10, 297–303 (1996).

    Google Scholar 

  69. Colacino, J.M. and Staschke, K.A.: Prog. Drug Res. 50, 259–322 (1998).

    Article  PubMed  CAS  Google Scholar 

  70. Colledge, D., Locarnini, S. and Shaw, T.: Hepatology 26, 216–225 (1997).

    CAS  Google Scholar 

  71. Colonno, R.J., Innaimo, S.F., Seifer, M., Genovesi, E., Clark, J., Yamanaka, G., Hamatake, R., Terry, B., Standring, D., Bisacchi, G., Sundeen, J. and Zahler, R.: Antiviral Res. 34, A51 (1997).

    Google Scholar 

  72. Colonno, R.J., Genovesi, E.V., Medina, I., Lamb, L., Durham, S., Corey, L., Locarnini, S., Tennant, B.C. and Clark, J.M.: 40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abst. 172 (2000).

    Google Scholar 

  73. Condreay, L.D., Jansen, R.W., Powdrill, T.F., Johnson, L.C., Selleseth, D.W., Paff, M.T., Daluge, S.M., Painter, G.R., Furman, P.A., Ellis, M.N. and Averett, D.R.: Antimicrob. Agents Chemother. 38, 616–619 (1994).

    Article  PubMed  CAS  Google Scholar 

  74. Condreay, L.D., Condreay, J.P., Jansen, R.W., Paff, M.T. and Averett, D.R.: Antimicrob. Agents Chemother. 40, 520–523 (1996).

    PubMed  CAS  Google Scholar 

  75. Cui, L., Yoon, S., Schinazi, R.F. and Sommadossi, J.P.: J. Clin. Inv. 95, 555–563 (1995).

    Article  CAS  Google Scholar 

  76. Cui L., Schinazi, R.F., Gosselin, G., Imbach, J.L., Chu, C.K., Rando, R.F., Revankar, G.R., Sommadossi, J.P.: Bioch. Pharm. 52, 1577–1584 (1996).

    Article  CAS  Google Scholar 

  77. Cullen, J.M., Smith, S.L., Davis, M.G., Dunn, S.E., Botteron, C., Cecchi, A., Linsey, D., Linzey, D., Frick, L., Paff, M.T., Goulding, A. and Biron, K. Antimicrob. Agents Chemother. 41, 2076–2082 (1997).

    PubMed  CAS  Google Scholar 

  78. Cundy, K.C., Fishback, J.A., Shaw, J.P., Lee, M.L., Soike, K.F, Visor, G.C. and Lee, W.A.: Pharm. Res. 11, 839–843 (1994).

    Article  PubMed  CAS  Google Scholar 

  79. Dannaoui, E., Trepo, C. and Zoulim, F.: Antiviral Chem. Chemother. 8, 38–46 (1997).

    CAS  Google Scholar 

  80. Davis, M.G., Wilson, J.E., Van Draanen, N.A., Miller, W.H., Freeman, G.A., Daluge, S.M., Boyd, F.L., Aulabaugh, A.E., Painter, F.R. and Boone, L.R.: Antiviral Res. 30, 133–145 (1996).

    Article  CAS  Google Scholar 

  81. De Clercq, E.: AIDS Res. Human Retroviruses 8, 119–134 (1992).

    Article  Google Scholar 

  82. de Man, R.A., Marcellin, P., Habgal, F., Desmond, P., Wright, T., Rose, T., Jurewicz, R. and Young, C.: Hepatology 32, 413–417 (2000).

    Article  CAS  Google Scholar 

  83. Denes A.E., Ebert, J.W., Berquist, K.R, Murphy, B.L. and Maynard, J.E.: Antimicrob. Agents Chemother. 10, 571–572 (1976).

    Article  PubMed  CAS  Google Scholar 

  84. DeNoon, D.J.: Hepatitis Weekly, October 21, 1996.

    Google Scholar 

  85. Dienstag, J.L., Perrillo, R.P., Schiff, E.R, Bartholomew, M., Vicary, C., Rubin, M.: J. Hepatology 20, 199A (1994).

    Google Scholar 

  86. Dienstag, J.L., Schiff, E.R., Mitchell, M., Casey, D.E. Jr., Gitlin, N., Lissoos, T., Gelb, L.D., Condreay, L., Crowther, L., Rubin, M. and Brown, N.: Hepatology 30, 1082–1087 (1999).

    Article  CAS  Google Scholar 

  87. Doong, S.L., Tsai, C.H., Schinazi R.F., Liotta, D.C. and Cheng Y.C.: Proc. Natl. Acad. Sci. USA 88, 8495–8499 (1991).

    Article  CAS  Google Scholar 

  88. El Alaoui, A.M., Faraj, A., Pierra, C., Boudou, V., Johnson, R., Mathe, C., Gosselin G., Korba, B.E., Imbach, J.L., Schinazi R.F. and Sommadossi, J.P.: Antiviral Chem. Chemother. 7, 276–280 (1996).

    Google Scholar 

  89. Elion, G.B.: J. Med. Virol. Suppl. 1, S2 - S6 (1993).

    Article  Google Scholar 

  90. Enriquez, P.M., Jung, C., Josephson, L. and Tennant, B.C.: Bioconjugate Chem. 6, 195–202 (1995).

    Article  CAS  Google Scholar 

  91. Eriksson, B. and Oberg, B., in: Becker, Y. (ed.): Antiviral Drugs and Interferon, Martinus Nijhoff Publishing, Boston 1984, pp. 127–142.

    Chapter  Google Scholar 

  92. Etta, L.V., Brown, J., Mastri, A. and Wilson, T.: J. Am. Med. Assoc. 246, 1073–1075 (1981).

    Article  Google Scholar 

  93. Fanucchi, M.P., Leyland-Jones, B., Young, C.W., Burchenal, J.H., Watanabe, K.A., Fox, J.J.: Cancer Treat. Rpts. 69, 55–59 (1985).

    CAS  Google Scholar 

  94. Farquhar, D., Kahn, S., Srivastva, D.N., Saunders, P.P.: J. Med. Chem. 37, 3902–3909 (1994).

    Article  PubMed  CAS  Google Scholar 

  95. Farza, H., Hadchouel, M., Scotto, J., Tiollais, P., Babinet, C. and Pourcel, C.: J. Virol. 62, 4144–4152 (1988).

    PubMed  CAS  Google Scholar 

  96. Feitelson, M.A., Millman, I., Halbherr, T., Simmons, H. and Blumberg, B.S.: Proc. Natl. Acad. Sci. USA 83, 2233–2237 (1986).

    Article  CAS  Google Scholar 

  97. Feitelson, M.A., Millman, I. and Blumberg, B.S.: Proc. Natl. Acad. Sci. USA. 83, 2994–2997 (1986).

    Article  CAS  Google Scholar 

  98. Field, A.K. and Goodchild, J.: Exp. Opin. Invest. Drugs 4, 799–821 (1995).

    Article  CAS  Google Scholar 

  99. Field, A.K., Davies, M.E., DeWitt, C., Perry, H.C., Liou, R., Germershausen, J., Karkas, J.D., Ashton, W.T., Johnston, D.B.R. and Tolman, R.L.: Proc. Natl. Acad. Sci. USA 80, 4139–4143 (1983).

    Article  CAS  Google Scholar 

  100. Fischer, K.P. and Tyrrell, D.L.J.: Antimicrob. Agents Chemother. 40, 1957–1960 (1996).

    PubMed  CAS  Google Scholar 

  101. Fiume, L., Busi, C., Mattioli, A., Balboni, P.G., Barbanti-Brodano, G.: FEBS Lett. 129, 261–264 (1981).

    Article  CAS  Google Scholar 

  102. Fiume, L., Bassi, B., Busi, C., Mattioli, A. and Spinosa, G.: Biochem. Pharmacol. 35, 967–972 (1986).

    Article  PubMed  CAS  Google Scholar 

  103. Fiume, L., Bassi, B., Busi, C., Mattioli, A., Sinosa, G. and Faulstich, H.: FEBS Lett. 203, 203–206 (1986).

    Article  CAS  Google Scholar 

  104. Fleet, G.W., Karpas, A., Dwek, R.A., Fellows, L.E., Tyms, A.S., Petursson, S., Namgoong, S.K., Ramsden, N.G., Smith, P.W., Son, J.C., Wilson, E, Witty, D.R., Jacob, G.S. and Radenmacher, T.W.: FEBS Lett. 237, 128–132 (1988).

    Article  CAS  Google Scholar 

  105. Fontana, R.J. and Lok, A.S.F.: Hepatology 26, 234–237 (1997).

    Article  PubMed  CAS  Google Scholar 

  106. Fourel, I., Hantz, O., Cova, L., Allaudeen, H.S. and Trepo, C.: Antimicrob. Agents Chemother. 34, 473–475 (1990).

    Article  PubMed  CAS  Google Scholar 

  107. Fourel, I., Li, J., Hantz, O., Jacquet, C., Fox, J.J. and Trepo, C.: J. Med. Virol. 37, 122–126 (1992).

    Article  PubMed  CAS  Google Scholar 

  108. Fourel, I., Saputelli, J., Schaffer, P.A. and Mason, W.S.: J. Virol. 68, 1059–1065 (1994).

    PubMed  CAS  Google Scholar 

  109. Fox, J.J., Watanabe, K.A., Chou, T.C., Schinazi R.F., Soike, K.F., Fourel, I., Hantz, O. and Trepo, C.: Taylor, F.N. (ed.): Fluorinated Carbohydrates, Chemical and Biochemical Aspects, American Chemical Society, Washington, D.C. 1988, pp. 176–190.

    Google Scholar 

  110. Fried, M.W., Di Bisceglie, A.M., Straus, S.E., Savarese, B., Beames, M.P. and Hoofnagle, J.H.: Hepatology 16, 127a (1992).

    Article  Google Scholar 

  111. Fried, M.W., Fong, T.L., Swain, M.G., Beames, P.Y., Banks, S.M., Hoofnagle, J.H., Di Bisceglie, A.M.: J. Hepatology 21, 145–150 (1994).

    Article  CAS  Google Scholar 

  112. Fu, L., Liu, S.H. and Cheng, Y.C.: Biochem. Pharmacol. 57, 1351–1359 (1999).

    Article  PubMed  CAS  Google Scholar 

  113. Furman, P.A., Davis, M., Liotta, D.C., Paff, M., Frick, L.W., Nelson, D.J., Dornsife, R.E., Wurster, J.A., Wilson, L.J., Fyfe, J.A., Tuttle, J.V., Miller, W.H., Condreay, L., Averett, D.R., Schinazi, R.F. and Painter, G.R.: Antimicrob. Agents Chemother. 36, 2686–2692 (1992).

    Article  PubMed  CAS  Google Scholar 

  114. Furman, P.A., Wilson, J.E., Reardon, J.E. and Painter, G.R.: Antiviral Chem. Chemother. 6, 345–355 (1995).

    CAS  Google Scholar 

  115. Galle, P.R., Schlicht, H.J., Fischer, M., Schaller H.: 1988. Production of infectious duck hepatitis B virus in a human hepatoma cell line. J. Virol. 62, 1736–1740 0.

    CAS  Google Scholar 

  116. Galle, P.R., Schlicht H.J., Kuhn, C., Schaller, H.: Hepatology 10, 459–465 (1989).

    Article  PubMed  CAS  Google Scholar 

  117. Galun, E., Nahor, O., Eid, A., Jurim, O., Rose-John, S., Blum, H.E., Nussbaum, O., Ilan, E., Daudi, N., Shouval, D. et al.: Virology 270, 299–309 (2000).

    Article  PubMed  CAS  Google Scholar 

  118. Ganem, D., in: Fields, B.N., Knipe, D.M., Howley, P.M. (eds.): Virology, Lippincott-Raven Publishers, Philadelphia 1996, pp. 2703–2737.

    Google Scholar 

  119. Ganem, D. and Varmus, H.E.: Annu. Rev. Biochem. 56, 651–693 (1987).

    Article  PubMed  CAS  Google Scholar 

  120. Gao, H.Q., Boyer, P.L., Sarafianos, S.G., Arnold, E. and Hughes, S.H.: J. Mol. Biol. 300, 403–418 (2000).

    Article  PubMed  CAS  Google Scholar 

  121. Genovesi, E.V., Lamb, L., Medina, I., Taylor, D., Seifer, M., Innaimo, S., Colonno, R.J., Standring, D.N. and Clark, J.M.: Antimicrob. Agents Chemother. 42, 3209–3217 (1998).

    PubMed  CAS  Google Scholar 

  122. Gilson, R.J.C., Chopra, K.B., Newell, A.M., Murray-Lyon, I.M., Nelson, M.R., Rice, S.J., Tedder, R.S., Toole, J., Jaffe, H.S. and Weller, I.V.: J. Viral Hep. 6, 387–395 (1999).

    Article  CAS  Google Scholar 

  123. Gish, R.G., Lau, J.Y., Brooks, L., Fang, J.W., Steady, S.L., Imperial, J.C., Garcia-Kennedy R., Esquivel, C.O. and Keeffe, E.B.: Hepatology. 23, 1–7 (1996).

    Article  CAS  Google Scholar 

  124. Gojobori, T. and Yokoyama, S.: Proc. Natl. Acad. Sci. USA 82, 4198–4201 (1985).

    Article  CAS  Google Scholar 

  125. Gojobori, T., Moriyama, E.N. and Kimura, M.: Proc. Natl. Acad. Sci. USA 87, 10015–10018 (1990).

    Article  CAS  Google Scholar 

  126. Goodarzi G., Gross, S.C., Tewari, A. and Watabe, K.: J. Gen. Virol. 71, 3021–3025 (1990).

    Article  PubMed  CAS  Google Scholar 

  127. Grant, A.J., Feinberg, A., Chou, T.C., Watanabe, K.A., Fox, J.J. and Philips, F.S.: Bioch. Pharmacol. 31, 1103–1108 (1982).

    Article  CAS  Google Scholar 

  128. Grellier, L., Mutimer, D., Ahmed, M., Brown, D., Burroughs, A.K., Rolles, K., McMaster, P., Beranek, P., Kennedy, E, Kibbler, H., McPhillips, P., Elias, E. and Dushieko, G.: Lancet 348, 1212–1215 (1996).

    Article  CAS  Google Scholar 

  129. Gripon, P., Diot, C., Theze, N., Fourel, I., Loreal, O., Brechot, C., Guguen-Guillouzo, C.: J. Virol. 62, 4136–4143 (1988).

    PubMed  CAS  Google Scholar 

  130. Guidotti, L.G., Matzke, B., Pasquinelli, C., Schoenberger, J.M., Rogler, C.E., Chisari, F.V.: J. Virol. 70, 7056–7061 (1996).

    PubMed  CAS  Google Scholar 

  131. Hagelstein, J., Fathinejad, E, Stemmel, W. and Galle, P.R.: Virology 229, 292–294 (1997).

    Article  PubMed  CAS  Google Scholar 

  132. Hagmeyer, K.O. and Pan, Y.Y.: Annals Pharmacother. 33, 1104–1112 (1999).

    Article  CAS  Google Scholar 

  133. Hantz, O., Allaudeen, H.S., Ooka, T., De Clercq, E. and Trepo, C.: Antiviral Res. 4, 187–199 (1984).

    Article  CAS  Google Scholar 

  134. Harrell, A.W., Wheeler, S.M., Pennick, M., Clarke, S.E., Chenery, R.J.: Drug Met. Disp. 21, 18–23 (1993).

    CAS  Google Scholar 

  135. Heathcote, J., McHutchison, J., Benner, K., Wright, T., Minuk, G., Sacks, S., Sherman, M., Rustgi, V., Perrillo, R., King, P., Redeker, A., Davis, G., Lok, A. and Chesnut, R.: Hepatology 24, 283A (1996).

    Google Scholar 

  136. Heijtink, R.A., De Wilde, G.A., Kruining, J., Berk, L., Balzarini, J., De Clercq, E., Holy, A. and Schalm, S.W.: Antiviral Res. 21, 141–153 (1993).

    Article  CAS  Google Scholar 

  137. Helgstrand, E., Eriksson, B., Johansson, N.G., Lannero, B., Larsson, A., Misiorny, A., Noren, J.O., Sjoberg, B., Stenberg, K., Stening, G., Stridh, S. and Oberg, B.: Science 201, 819–821 (1978).

    CAS  Google Scholar 

  138. Hess, G., Arnold, W. and Meyer zum Buschenfelde, K.H.: J. of Med. Virol. 5, 309–316 (1980).

    Article  CAS  Google Scholar 

  139. Hino, O., Nomura, K., Ohtake, K., Saito, I., Abe, K., Rogler, C.E., Sugano, H. and Kitagawa, T.: Gastroenterologia Japonica 25, (Suppl. 2), 53–56 (1990).

    Google Scholar 

  140. Hirota, K., Sherker, A.H., Omata, M., Yokosuka, O., Okuda, K.: Hepatology 7, 24–28 (1987).

    Article  PubMed  CAS  Google Scholar 

  141. Honkoop, P., de Man, R.A., Zondervan, P.E. and Schalm, S.W.: Liver 17, 103–106 (1997).

    PubMed  CAS  Google Scholar 

  142. Honkoop, P., de Man, R.A., Scholte, H.R., Zondervan, P.I., van den Berg, J.W.O., Rademakers, L.H.P.M. and Schalm, S.W.: Hepatology 26, 211–215 (1997).

    Article  PubMed  CAS  Google Scholar 

  143. Honkoop, P., Niesters, H.G.M., De Man, R.A., Osterhaus, A.D.M.E. and Schalm, S.W.: c. J. Hepatology 26, 1393–1395 (1997).

    Article  CAS  Google Scholar 

  144. Honkoop, P., Scholte, H.R., de Man, R.A. and Schalm, S.W.: Drug Safety 17, 1–7 (1997).

    Article  CAS  Google Scholar 

  145. Hoofnagle, J.H., Di Bisceglie, A.M.: N. Engl. J. Med. 336, 347–356 (1997).

    Article  PubMed  CAS  Google Scholar 

  146. Hoofnagle, J.H., Lau, D.: N. Engl J. Med. 334, 1470–1471 (1996).

    Article  PubMed  CAS  Google Scholar 

  147. Hoofnagle, J.H., Dushieko, G.M., Seeff, L.B., Jones, E.A., Waggoner, J.G., Bales, Z.B.: Ann. Intern. Med. 94, 744–748 (1981).

    PubMed  CAS  Google Scholar 

  148. Hoofnagle, J.H., Minuk, G.Y., Dusheiko, G.M., Schafer, D.F., Johnson, R., Straus, S., Jones, E.A., Gerin, J.L. and Ishak, K.: Hepatology 2, 784–788 (1982).

    Article  CAS  Google Scholar 

  149. Hoofnagle, J.H., Hanson, R.G., Minuk, G.Y., Pappas, S.C., Schafer, D.F., Dusheiko, G.M., Straus, S.E., Popper, H. and Jones, E.: Gastroenterology 86, 150–157 (1984).

    CAS  Google Scholar 

  150. Hoofnagle, J.H., Davis, G.L., Hanson, R.G., Pappas, S.C, Peters, M.G., Avigan, M.I., Wag- goner J.G., Howard, R., Jones, E.A. and Straus, S.E.: J. Med. Virol. 15, 121–128 (1985).

    Article  PubMed  CAS  Google Scholar 

  151. Hostetler, K.Y., Beadle, J.R., Hornbuckle, W.E., Bellezza, C.A., Tochkov, I.A., Cote, P.J., Gerin, J.L., Korba, B.E. and Tennant, B.C.: Antimicrob. Agents Chemother. 44, 1964–1969 (2000).

    Article  PubMed  CAS  Google Scholar 

  152. Hostetler, KY, Beadle, J.R., Kini, G.D., Gardner, M.F., Wright, K.N, Wu, T.H. and Korba, B.A.: Biochem. Pharmacol. 53, 1815–1822 (1997).

    Article  PubMed  CAS  Google Scholar 

  153. Howe, A.Y.M., Elliott, J.F. and Tyrrell, D.L.J.: Bioch. Biophys. Res. Comm. 189, 1170–1176 (1992).

    Article  CAS  Google Scholar 

  154. Hu, J. and Seeger, C.: Proc. Natl. Acad. Sci. USA 93, 1060–1064 (1996).

    Article  CAS  Google Scholar 

  155. Hu, J., Toft, D.O. and Seeger, C.: EMBO J. 16, 59–68 (1997).

    Article  Google Scholar 

  156. Hudson, J.B., Lopez-Bazzocchi, I. and Towers, G.H.N.: Antiviral Res. 15, 101–112 (1991).

    Article  CAS  Google Scholar 

  157. Ikeda, N., Kaneko, S., Shimoda, A., Inagaki, Y., Unoura, M., Yonekawa, Y., Takahasi, K. and Kobayashi, K.: J. Animicrob. Chemother. 33, 83–89 (1994).

    Article  CAS  Google Scholar 

  158. Innaimo, S.F., Seifer, M., Bisacchi, G.S., Standring, D.N., Zahler, R. and Colonno, R.J.: Antimicrob. Agents. Chemother. 41, 1444–1448 (1997).

    CAS  Google Scholar 

  159. Innaimo, S.F., Seifer, M., Bisacchi, G.S., Standring, D.N., Zahler, R., Colonno, R.J.: Antimicrob. Agents. Chemother. 41, 1444–1448 (1997).

    CAS  Google Scholar 

  160. Jacyna, M.R. and Thomas, H.C.: British Med. Bull. 46, 368–382 (1990).

    CAS  Google Scholar 

  161. Jarvis, B. and Faulds, D.: Drugs 58, 101–141 (1999).

    Article  PubMed  CAS  Google Scholar 

  162. Jilg, W., Schmidt, M., Deinhardt, F., Zachoval, R.: Lancet 2, 458 (1989).

    Google Scholar 

  163. Josefson, D.: BMJ 317, 1034 (1998).

    Article  PubMed  CAS  Google Scholar 

  164. Kakumu, S., Yoshioka, K., Wakita, T., Ishikawa, T., Takayanagi, M. and Higashi, Y.: Hepatology 18, 258–263 (1993).

    Article  CAS  Google Scholar 

  165. Karpas, A., Fleet, G.W., Dwek, R.A., Petursson, S., Namgoong, S.K., Ramsden, N.G., Jacob, G.S. and Rademacher, T.W.: Proc. Natl. Acad. Sci. USA 85, 9229–9233 (1988).

    Article  CAS  Google Scholar 

  166. Kassianides, C., Hoofnagle, J.H., Miller, R.H., Doo, E., Ford, H., Broder, S. and Mitsuya, H.: Gastroenterology 97, 1275–1280 (1989).

    PubMed  CAS  Google Scholar 

  167. Khudyakov, Y.E. and Makhov, A.M.: FEBS Lett. 243, 115–118 (1989).

    Article  PubMed  CAS  Google Scholar 

  168. Klecker, R.W., Katki, A.G., Collins, J.M.: Mol. Pharmac. 46, 1204–1209 (1994).

    CAS  Google Scholar 

  169. Klein, N.P., Bouchard, M.J., Wang, L.H., Kobarg, C. and Schneider, R.J.: EMBO 18, 50195027 (1999).

    Google Scholar 

  170. Klein, M., Geoghegan, J., Schmidt, K., Bockler, D., Korn, K., Wittekind, C., Scheele, J.:. Transplantation 64, 162–163 (1997).

    CAS  Google Scholar 

  171. Knaus, E.E., Parang, K., Wiebe, L.I., Huang, J.S. and Tyrrell, D.L.: J. Pharm Pharm. Sci. 1, 108–114 (1998).

    PubMed  Google Scholar 

  172. Kock, J., Borst, E.M. and Schlicht, H.J.: J. Virol. 70, 5827–5831 (1996).

    PubMed  CAS  Google Scholar 

  173. Kohlstaedt, L.A., Wang, J., Friedman, J.M., Rice, P.A. and Steitz, T.A.: Science 256, 1783–1790 (1992).

    Article  PubMed  CAS  Google Scholar 

  174. Korba, B.E., Cote, P., Hornbuckle, W., Schinazi, R., Gangemi, J.D., Tennant, B.C. and Gerin, J.L.: Antiviral Ther. 5, 95–104 (2000).

    CAS  Google Scholar 

  175. Korba, B.E.: Antiviral Res. 29, 49–51 (1996).

    Article  PubMed  CAS  Google Scholar 

  176. Korba, B.E. and Milman, G.: Antiviral Res. 15, 217–228 (1991).

    Article  PubMed  CAS  Google Scholar 

  177. Korba, B.E. and Gerin, J.L.: Antiviral Res. 17, 1–16 (1992).

    Article  Google Scholar 

  178. Korba, B.E. and Gerin, J.L.: Antiviral Res. 28, 225–242 (1995).

    Article  PubMed  CAS  Google Scholar 

  179. Korba, B.E., Cote, P.J., Tennant, B.C. and Gerin, J.L., in: Hollinger, F.B., Lemon, S.M. and Margolis, H.S. (eds.): Viral Hepatitis and Liver Disease, Williams and Williams, Baltimore 1991, pp. 663–665.

    Google Scholar 

  180. Korba, B.E., Schinazi, R.F., Cote, P., Tennant, B.C. and Gerin, J.L.: Antimicrob. Agents Chemother. 44, 1757–1760 (2000).

    Article  PubMed  CAS  Google Scholar 

  181. Kreis, W., Damin, L., Colacino, J., Lopez, C.: Biochem. Pharm. 31, 767–773 (1982).

    Article  PubMed  CAS  Google Scholar 

  182. Kufe, D.W., Major, P.P., Egan, E.M. and Beardsley, G.P.: J. Biol. Chem. 255, 8997–9000 (1980).

    PubMed  CAS  Google Scholar 

  183. Kukhanova, M., Lin, Z.Y., Yas’co, M. and Cheng, Y.C.: Biochem. Pharmacol. 55, 11811187 (1998).

    Google Scholar 

  184. Kukhanova, M., Liu, S.H., Mozzherin, D., Lin, T.S., Chu, C.K. and Cheng, Y.C.: J. Biol. Chem. 270, 23055–23059 (1995).

    Article  PubMed  CAS  Google Scholar 

  185. Kuroki, K., Cheung, R., Marion, P.L. and Ganem, D.: J. Virol. 68, 2091–2096 (1994).

    PubMed  CAS  Google Scholar 

  186. Kuroki, K., Eng, F., Ishikawa, T., Turck, C., Harada, F. and Ganem, D.: J. Biol. Chem. 270, 15022–15028 (1995).

    Article  PubMed  CAS  Google Scholar 

  187. Ladner, S.K., Miller, T.J., Otto, M.J. and King, R.W.: Antiviral Chem Chemother. 9, 65–72 (1998).

    CAS  Google Scholar 

  188. Ladner, S.K., Otto, M.J., Marker, C.S., Zaifert, K., Wang, G.H., Guo, J.T., Seeger, C. and King, R.W.: Antimicrob. Agents Chemother. 41, 1715–1720 (1997).

    PubMed  CAS  Google Scholar 

  189. Lai, C.L., Ching, C.K., Tung, A.K.M., Li, E., Young, J., Hill, A., Wong, B.C.Y., Dent, J. and Wu, P.C.: Hepatology 25, 241–244 (1997).

    Article  PubMed  CAS  Google Scholar 

  190. Lamberts, C., Nassal, M., Velhagen, I., Zentgraf, H., Schroeder, C.H.: J. Virol. 67, 3756–3762 (1993).

    PubMed  CAS  Google Scholar 

  191. Lampertico, P., Malter, J.S. and Gerber, M.A.: Hepatology 13, 422–426 (1991).

    CAS  Google Scholar 

  192. Lanford, R.E., Chavez, D., Brasky, K.M., Burns, R.B. III. and Rico-Hesse, R.: Proc. Natl. Acad. Sci USA 95, 5757–5761 (1998).

    Article  CAS  Google Scholar 

  193. Lanford, R.E., Chavez, D., Rico-Hesse, R. and Mootnick, A.: J. Virol. 74, 2955–2959 (2000).

    Article  PubMed  CAS  Google Scholar 

  194. Lanford, R.E., Notvall, L. and Beames, B.: J. Virol. 69, 4431–4439 (1995).

    PubMed  CAS  Google Scholar 

  195. Lanford, R.E., Michaels, M.G., Chavez, D., Brasky, K., Fung, J. and Starzl, T.E.: J. Med. Virol. 46, 207–212 (1995).

    Article  PubMed  CAS  Google Scholar 

  196. Lau, D.T., Farooq Khokhar, M., Doo, E., Ghany, M.G., Herion, D., Park, Y., Kleiner, D., Schmid, P., Condreay, L.D., Gaulthier, J. et al.: Hepatology 32, 828–834 (2000).

    Article  PubMed  CAS  Google Scholar 

  197. Lavie, G., Mazur, Y., Lavie, D., Prince, A.M., Pascual, D., Liebes, L., Levin, B. and Meru- elo, D.: Transfusion 35, 392–400 (1995).

    Article  CAS  Google Scholar 

  198. Lee, B., Luo, W.X., Suzuki, S., Robins, M.J. and Tyrrell, D.L.: Antimicrob. Agents Chemother. 33, 336–339 (1989).

    Article  PubMed  CAS  Google Scholar 

  199. Lee, C.D., Ott, M., Thyagarajan, S.P., Shafritz, D.A., Burk, R.D. and Gupta, S.: Eur. J. Clin. Invest. 26, 1069–1076 (1996).

    Article  PubMed  CAS  Google Scholar 

  200. Lee, Y.I., Hong, Y.B., Kim, Y., Rho, H.M. and Jung, G.: Biochem. Biophys. Res. Comm. 233, 401–407 (1997).

    Article  CAS  Google Scholar 

  201. Leinbach, S.S., Reno, J.M., Lee, L.F., Isbell, A.F. and Boezi, J.A.: Biochem. 15, 426–430 (1976).

    Article  CAS  Google Scholar 

  202. Levine, A.J.: Viruses. The hepatitis B virus, Scientific American Library, New York, New York 1992, pp. 177–193.

    Google Scholar 

  203. Lewis, W., Meyer, R.R., Simpson, J.F., Colacino, J.M., Perrino, F.W.: Biochemistry 33, 14620–14624 (1994).

    Article  PubMed  CAS  Google Scholar 

  204. Lewis, W., Levine, E.S, Griniuviene, B., Tankersley, K.O, Colacino, J.M., Sommadossi, J.P., Watanabe, K.A. and Perrino, F.W.: Proc. Natl. Acad. Sci. USA 93, 3592–3597 (1996).

    Article  CAS  Google Scholar 

  205. Li, J., Tong, S. and Wands, J.R.: J. Virol. 70, 6029–6035 (1996).

    PubMed  CAS  Google Scholar 

  206. Li, J., Tong, S. and Wands, J.R.: J. Biol. Chem. 274, 27658–27665 (1999).

    Article  PubMed  CAS  Google Scholar 

  207. Liaw, Y.F., Chu, C.M., Su, I.J., Huang, M.J., Lin, D.Y. and Chang-Chien, C.S.: Gastroenterology 84, 216–219 (1983).

    CAS  Google Scholar 

  208. Lieberman, K.C. and Heidelberger, C.: J. Biol. Chem. 316, 823–830 (1955).

    Google Scholar 

  209. Lin, E., Luscombe, C., Wang, Y.Y., Shaw, T. and Locarnini, S.: Antimicrob. Agents Chemother. 40, 413–418 (1996).

    PubMed  CAS  Google Scholar 

  210. Lin, J.C., Smith, M.C. and Cheng, Y.C.: Science 221, 578–579 (1983).

    Article  CAS  Google Scholar 

  211. Lin, T.S., Luo, M.Z., Liu, M.C., Pai, S.B., Dutschman, G.E. and Cheng, Y.C.: Biochem. Pharm. 47, 171–174 (1994).

    PubMed  CAS  Google Scholar 

  212. Lin, T.S., Luo MZ, Zhu J.L., Liu MC, Zhu YL., Dutschman GE, Cheng YC.: 1995. Synthesis of a series of purine 2’,3’-dideoxy-L-nucleoside analogues as potential antiviral agents. Nucleosides Nucleotides 14, 1759–1783 0.

    CAS  Google Scholar 

  213. Lin, T.S., Luo, M.A., Liu, M.C., Zhu, Y.L., Gullen, E., Dutschman, G.E. and Cheng, Y.C.: J. Med. Chem. 39, 1757–1759 (1996).

    Article  PubMed  CAS  Google Scholar 

  214. Ling, R., Mutimer, D., Ahmend, M., Boxall, E.H., Elias, E., Dushieko, G.M. and Harrison, T.J.: Hepatology 24, 711–713 (1996).

    Article  CAS  Google Scholar 

  215. Liu, S.H., Grove, K.L. and Cheng, Y.C.: Antimicrob. Agents Chemother. 42, 833–839 (1998).

    PubMed  CAS  Google Scholar 

  216. Livingston, B.D., Crimi, C., Grey, H., Ishioka, G., Chisari, F.V., Fikes, J., Grey, H., Chesnut, R.W. and Sette, A.: J. Immunol. 159, 1383–1392 (1997).

    PubMed  CAS  Google Scholar 

  217. Lofgren, B., Vickery, K., Zhang, Y.Y. and Nordenfelt, E.: J. Viral Hep. 3, 61–65 (1996).

    Article  CAS  Google Scholar 

  218. Lofgren, B., Habteyesus, A., Nordenfelt, E., Eriksson, S. and Oberg, B.: Antiviral Chem. Chemother. 1, 361–366 (1990).

    Google Scholar 

  219. Lofgren, B., Nordenfelt, E. and Oberg, B.: Antiviral Res. 12, 301–310 (1989).

    Article  PubMed  CAS  Google Scholar 

  220. Lok, A.S.: Gastroenterol. 119, 263–266 (2000).

    Article  CAS  Google Scholar 

  221. Lopez, C., Watanabe, K.A. and Fox, J.J.: Antimicrob. Agents Chemother. 17, 803–806 (1980).

    Article  PubMed  CAS  Google Scholar 

  222. Lopez-Bazzochi, I., Hudson, J.B. and Towers, G.H.N.: Photochem. Photobiol. 54, 95–98 (1991).

    Article  Google Scholar 

  223. Lu, X., Block, T.M. and Gerlach, W.H.: J. Virol. 70, 2277–2285 (1996).

    PubMed  CAS  Google Scholar 

  224. Lu, X., Mehta, A., Dadmarz, M., Dwek, R., Blumberg, B.S. and Block, T.M.: Proc. Natl. Acad. Sci. USA 94, 2380–2385 (1997).

    Article  CAS  Google Scholar 

  225. Luscombe, C., Pedersen, J., Uren, E. and Locarnini, S.: Hepatology. 24, 766–773 (1996).

    PubMed  CAS  Google Scholar 

  226. Ma, T., Pai, S.B., Zhu, Y.L., Lin, J.S., Shanmuganathan, K., Du, J., Wang, C., Kim, H., Newton, M.G., Cheng, Y.C. and Chu, C.K.: J. Med. Chem. 39, 2835–2843 (1996).

    Article  PubMed  CAS  Google Scholar 

  227. Macrae, D.R., Bruss, V. and Ganem, D.: Virology 181, 359–63 (1991).

    Article  CAS  Google Scholar 

  228. Main, J., Brown, J.L., Howells, C., Galassini, R., Crossey, M., Karayiannis, P., Gerogiou, P., Atkinson, G. and Thomas, H.C.: J. Viral. Hepatitis 3, 211–215 (1996).

    Article  CAS  Google Scholar 

  229. Malik, A.H. and Lee, W.M.: Annals Intern. Med. 132, 723–731 (2000).

    CAS  Google Scholar 

  230. Mansour, T.S., Tse, A. and Charron, M.: Med. Chem. Res. 5, 417–425 (1995).

    CAS  Google Scholar 

  231. Mansour, T.S. and Storer, R.: Curr. Pharm. Design 3, 227–264 (1997).

    CAS  Google Scholar 

  232. Mao, J.C. and Robishaw, E.E.: Biochem. 14, 5475–5479 (1975).

    Article  CAS  Google Scholar 

  233. Margolis, H.S., Alter, M.J. and Haider, S.C.: Semin. Liv. Dis. 11, 84–92 (1991).

    Article  CAS  Google Scholar 

  234. Marshall, J.S., Williams, S. and Jones, P.: J. Lab. Clin. Med. 92, 30–37 (1978).

    PubMed  CAS  Google Scholar 

  235. Mason, W.S., Cullen, J., Saputelli, J., Wu, T.T., Liu, C., London, W.T., Lustbader, E., Schaffer, P., O’Connell, A.P., Fourel, I., Aldrich, C.E. and Jilbert, A.R.: Hepatology.: 19, 398–411 (1994).

    Article  CAS  Google Scholar 

  236. Matthes, E., Langen, P., von Janta-Lipinski, M., Will, H., Schroeder, H.C., Merz, H., Weiler, B.E. and Muller, W.E.G.: Antimicrob. Agents Chemother. 34, 1986–1990 (1990).

    Article  PubMed  CAS  Google Scholar 

  237. McKenzie, R., Fried, M.W., Sallie, R., Conjeevaram, H., Di Bisceglie, A.M., Park, Y., Savarese, B., Kleiner, D., Tsokos, M., Luciano, C., Pruett, T., Stotka, J.L., Straus, S.E. and Hoofnagle, J.H.: N. Engl. J. Med. 333, 1099–1105 (1995).

    Article  PubMed  CAS  Google Scholar 

  238. Mehrotra, R.and Srivastava, S.: Ind. J. Med. Res. 85, 113–119 (1987).

    Google Scholar 

  239. Mehta, A., Lu, X., Block, T.M., Blumberg, B.S. and Dwek, R.A.: Proc. Natl. Acad. Sci. USA 94, 1822–1827 (1997).

    Article  CAS  Google Scholar 

  240. Meijer, D.K.F. and Molema, G.: Semin. Liver. Dis. 15, 202–256 (1995).

    Article  PubMed  CAS  Google Scholar 

  241. Melegari, M., Scaglioni, P.P. and Wands, J.R.: Hepatology 27, 628–633 (1998).

    Article  PubMed  CAS  Google Scholar 

  242. Meruelo, D., Lavie G. and Lavie D.: Proc. Natl. Acad. Sci. USA 85, 5230–5234 (1988).

    Article  CAS  Google Scholar 

  243. Moraleda, G., Wu, T.T., Jilbert, A.R., Aldrich, C.E., Condreay, L.D., Larsen, S.H., Tang, J.C., Colacino, J.M. and Mason, W.S.: Antiviral Res. 20, 235–247 (1993).

    Article  CAS  Google Scholar 

  244. Muller, W.E.G., Maidhof, A., Taschner, H. and Zahn, R.K.: Biochem. Pharmacol. 26, 1071–1075 (1977).

    Article  PubMed  CAS  Google Scholar 

  245. Mutchnick, M.G., Appelman, H.D., Chung, H.T., Aragona, E., Guota, T.P., Cummings, G.D., Waggoner, J.G., Hoofnagle, J.H. and Shafritz, D.A.: Hepatology 14, 409–415 (1991).

    Article  CAS  Google Scholar 

  246. Mutchnick, M.G., Lindsay, K., Schiff, E., Cummings, G. and Appelman, H.D.: Gastroenterology 108, A1127 (1995).

    Google Scholar 

  247. Mutchnick, G.M., Lindsay, K.L., Schiff, E.R., Cummings, G.D., Appelman, H.D., Peleman, R.R., Silva, M., Roach, K.C., Simmons, E, Milstein, S. et al.:J. Viral Hepat. 6, 397–403 (1999).

    Article  CAS  Google Scholar 

  248. Naessens, L., Snoeck, R., Andrei, G., Balzarini, J., Neyts, J. and De Clercq, E.: Antiviral Chem. Chemother. 8, 1–23 (1997).

    Google Scholar 

  249. Nagahata, T., Araki, K., Yamamura, K. and Matsubara, K.: Antimicrob. Agents Chemother. 36, 2042–2045 (1992).

    Article  PubMed  CAS  Google Scholar 

  250. Nagahata, T., Kitagawa, M. and Matsubara, K.:Antimicrob. Agents Chemother. 38, 707–712 (1994).

    Article  CAS  Google Scholar 

  251. Nakazono, K., Ito, Y., Wu, C.H. and Wu, G.Y.: Hepatology. 23, 1297–303 (1996).

    CAS  Google Scholar 

  252. Newbold, J.E., Xin, H., Tencza, M., Sherman G., Dean, J., Bowden, S. and Locarnini, S.: J. Virol. 69, 3350–3357 (1995).

    PubMed  CAS  Google Scholar 

  253. Nishiyama, Y., Yamamoto, N., Yamada, Y., Fujioka, H., Shimada, N. and Takahashi, Y.: J. Antibiotics 42, 1308–1311 (1989).

    Article  CAS  Google Scholar 

  254. Niu, J., Wang, Y., Dixon, R., Bowden, S., Qiao, M., Einck, L. and Locarnini, S.: Antiviral Res. 21, 155–171 (1993).

    Article  PubMed  CAS  Google Scholar 

  255. Niu, J., Wang, Y., Qiao, M., Gowans, E., Edwards, P., Thyagarajan, S.P., Gust, I. and Locarnini, S.: J. Med. Virol. 32, 212–218 (1990).

    Article  PubMed  CAS  Google Scholar 

  256. Nommensen, F.E., Go, S.T. and Maclaren, D.M.: Lancet 2, 847–849 (1989).

    Article  CAS  Google Scholar 

  257. Nordenfelt, E., Oberg, B., Helgstrand, E. and Miller, E.: Acta Path. Microbiol. Scand. Sect. B. 88, 169–175 (1980).

    CAS  Google Scholar 

  258. Offensperger, W.B., Offensperger, S., Walter, E., Teubner, K., Igloi, G., Blum, H. and Gerok, W.: EMBO J. 12, 1257–1262 (1993).

    CAS  Google Scholar 

  259. Ornata, M. and Uchiumi, K.: J. Hepatology 3 (Suppl. 2), S65–69 (1986).

    Google Scholar 

  260. Oon, C.J., Chen, W.N., Lim, N., Koh, S., Lim, G.K., Leong, A.L., Tan, G.S.: Antiviral Res. 41, 113–118 (1999).

    Article  PubMed  CAS  Google Scholar 

  261. Orito, E., Mizokami, M., Ina, Y., Moriyama, N.E., Kameshima, N., Yamamoto, M. and Gojobori, T.: Proc. Natl. Acad. Sci. USA 86, 7059–7062 (1989).

    Article  CAS  Google Scholar 

  262. Ozer, A., Khaoustov, V.I., Mearns, M., Lewis, D.E., Genta, R.M., Darlington, G.J. and Yoffe, B.: Gastroenterology 110, 1519–1528 (1996).

    Article  PubMed  CAS  Google Scholar 

  263. Pai, S.B., Liu, S.H., Zhu, Y.L., Chu, C.K. and Cheng, Y.C.: Antimicrob. Agents Chemother. 40, 380–386 (1996).

    CAS  Google Scholar 

  264. Parang, K., Wiebe, L.I., Knaus, E.E., Huang, J.S., Tyrrell, D.L. and Csizmadia, F.: Antiviral Res. 34, 75–90 (1997).

    Article  CAS  Google Scholar 

  265. Parkin, D.M., Pisani, P., Munoz, N. and Ferlay, J.: Cancer Surv. 33, 5–33 (1999).

    Google Scholar 

  266. Perri, S. and Ganem, D.: J. Virol. 70, 6803–6809 (1996).

    PubMed  CAS  Google Scholar 

  267. Perrillo, R., Schiff, E., Yoshida, E., Statler, A., Hirsch, K., Wright, T., Gutfreund, K, Lamy, P. and Murray, A.: Hepatology 32, 29–34 (2000).

    Google Scholar 

  268. Persing, D.H., Varmus, H.E. and Ganem, D.: J. Virol. 61, 1672–1677 (1987).

    PubMed  CAS  Google Scholar 

  269. Petcu, D.J., Aldrich, C.J., Coates, L., Taylor, J.M. and Mason, W.S.: Virology 167, 385–392 (1988).

    CAS  Google Scholar 

  270. Petry, W., Erhardt, A., Heintges, T. and Haussinger, D.: Z. Gastroenterol. 38, 77–87 (2000).

    Article  PubMed  CAS  Google Scholar 

  271. Poch, O., Sauvaget, I., Delarue, M. and Tordo, N.: EMBO J. 8, 3867–3874 (1989).

    CAS  Google Scholar 

  272. Pollard, R.B., Smith, J.L., Neal, A., Gregory, P.B., Merigan, T.C. and Robinson, W.S.: J. Am. Med. Assoc. 239, 1648–1650 (1978).

    Article  CAS  Google Scholar 

  273. Ponzetto, A., Fiume, L., Forzani, B., Song, S.Y., Busi, C., Mattioli, A., Spinelli, C., Marinelli, M., Smedile, A., Chiaberge, E.F., Gervasi, G.B., Rapicetta, M. and Verme, G.: Hepatology 14, 16–24 (1991).

    Article  CAS  Google Scholar 

  274. Preiksaitis, J.K., Lan, K.B., Ng, P.K., Brox, L., LePage, G.A. and Tyrrell, D.L.J.: J. Inf. Dis. 144, 358–364 (1981).

    Article  CAS  Google Scholar 

  275. Price, P.M., Banerjee, R., Acs, G.: Proc. Natl. Acad. Sci. USA 86, 8541–8544 (1989).

    Article  CAS  Google Scholar 

  276. Price, P.M., Banerjee, R., Jeffrey, A.M. and Acs, G.: Hepatology 16, 8–12 (1992).

    Article  CAS  Google Scholar 

  277. Pugh, J.C. and Summers, J.W.: Virology 172, 564–572 (1989).

    Article  PubMed  CAS  Google Scholar 

  278. Qadri, I. and Siddiqui, A.: J. Biol. Chem. 274, 31359–31365 (1999).

    Article  PubMed  CAS  Google Scholar 

  279. Radziwill, G., Tucker, W. and Schaller, H.: J. Virol. 64, 613–620 (1990).

    PubMed  CAS  Google Scholar 

  280. Rajagopalan, P., Boudinot, F.D., Chu, C.K., Tennant, B.C., Baldwin, B.H. and Schinazi, R.F..: Antiviral Chem. Chemother. 7, 65–70 (1996).

    CAS  Google Scholar 

  281. Realdi G., Alberti, A., Rugge, M., Bortolotti, F., Rigoli, A.M., Tremolada, F. and Ruol, A.: Gastroenterology 79, 195–199 (1980).

    PubMed  CAS  Google Scholar 

  282. Reardon, J.E.: J. Biol. Chem. 264, 19039–19044 (1989).

    PubMed  CAS  Google Scholar 

  283. Rensen, P.C.N., de Vrueh, L.A., van Berkel, T.J.C.: Drug Delivery Systems 31, 131–155 (1996).

    CAS  Google Scholar 

  284. Richardson, F.C., Engelhardt, J.A. and Bowsher, R.R.: Proc. Natl. Acad. Sci. USA 91, 12003–12007 (1994).

    Article  CAS  Google Scholar 

  285. Rijintjes, P.J., Moshage, H.J. and Yap, S.H.: Virus. Res. 10, 95–110 (1988).

    Article  Google Scholar 

  286. Roll, P.M., Weinfeld, H., Carroll, E. and Brown, G.B.: J. Biol. Chem. 220, 439–454 (1956).

    PubMed  CAS  Google Scholar 

  287. Roome, A.J., Walsh, S.J., Cartter, M.L. and Hadler, J.L.: J. Am. Med. Assoc. 270, 2931–2934 (1993).

    Article  CAS  Google Scholar 

  288. Rosowsky, A., Saha, J., Fazely, F., Koch, J. and Ruprecht, R.: Biochem. Biophys. Res. Comm. 172, 288–293 (1990).

    Article  CAS  Google Scholar 

  289. Ryu, C.J., Cho, D.Y., Gripon, P., Kim, H.S., Guguen-Guillouzo, C. and Hong, H.J.: J. Virol. 74, 110–116 (2000).

    Article  PubMed  CAS  Google Scholar 

  290. Sacks, S.L., Smith, J.L., Pollard, R.B., Sawhney, V., Mahol, A.S., Gregory, P., Merigan, T.C. and Robinson, W.S.: J. Am. Med. Assoc. 241, 28–29 (1979).

    Article  CAS  Google Scholar 

  291. Sawamura, T., Nakada, H., Hazama, H., Shiozaki, Y., Sameshima, T. and Tashiro, Y.: Gastroenterology 87, 1217–1221 (1984).

    CAS  Google Scholar 

  292. Scaglioni, P.P., Melegari, M. and Wands, J.R.: Virology 205, 112–120 (1994).

    Article  CAS  Google Scholar 

  293. Scaglioni, P.P., Melegari, M. and Wands, J.R.: Bailliere’s Clinical Gastroenterology 10, 207–225 (1996).

    Article  CAS  Google Scholar 

  294. Scaglioni, P.P., Melegari, M., Takahashi, M., Chowdhury, J.R. and Wands, J.R.: Hepatology 24, 1010–1017 (1996).

    Article  CAS  Google Scholar 

  295. Scaglioni, P.P., Melegari, M. and Wands, J.R.: J. Virol. 71, 345–353 (1997).

    PubMed  CAS  Google Scholar 

  296. Schalm, S.W., Heijtink, R.A., Van Buuren, H.R. and de Man, R.A.:.J. Hepatology 3 (Suppl. 2), S189–192 (1986).

    Article  Google Scholar 

  297. Schalm, S.W., de Man, R.A., Heijtink, R.A. and Niesters, H.G.M.: J. Hepatology 22 (Suppl. 1), 52–56 (1995).

    Google Scholar 

  298. Schat, K.A., Schinazi, R.F. and Calnek, B.W.: Antiviral Res. 4, 259–270 (1984).

    Article  CAS  Google Scholar 

  299. Schilke, A.J., Staschke, K.A. and Colacino, J.M.: Antiviral Res. 23 (Suppl. 1), 80 (1994).

    Google Scholar 

  300. Schinazi, R.F., Fox, J.J., Watanabe, K.A. and Nahmias, A.J.: Antimicrob Agents Chemother. 29, 77–84 (1986).

    Article  CAS  Google Scholar 

  301. Schinazi, R.F., Chu, C.K., Babu, J.R., Oswald, B.J., Saalman, V., Cannon, D.L., Eriksson, B.F.H. and Nasr, M.: Antiviral Res. 13, 265–272 (1990).

    Article  CAS  Google Scholar 

  302. Schinazi, R.F., Lloyd, R.M. Jr., Nguyen, M.H., Canon, D.L., McMillan, A., Ilksoy, N., Chu, C.K., Liotta, D.C., Bazmi, H.Z. and Mellors, J.W.: Antimicrob. Agents Chemother. 37, 875–881 (1993).

    Article  PubMed  CAS  Google Scholar 

  303. Schinazi, R.F., McClure, H.M., Boudinot, F.D., Jxiang, Y. and Chu, C.K.: Antiviral Res. 23 (Suppl), 81 (1994).

    Google Scholar 

  304. Schinazi, R.F., Gosselin, G., Faraj, A., Korba, B.E., Liotta, D.C., Chu, C.K., Mathe, C., Imbach, J.L. and Sommadossi, J.P.: Antimicrob. Agents Chemother. 38, 2172–2174 (1994).

    Article  PubMed  CAS  Google Scholar 

  305. Schlicht, H.J., Radziwill, G. and Schaller, H.: Cell. 56, 85–92 (1989).

    Article  CAS  Google Scholar 

  306. Schreiber, G.B., Busch, M.P., Kleinman, S.H. and Korelitz, J.J. and The Retrovirus Epidemiology Donor Study: N. Engl. J. Med. 334, 1685–1690 (1996).

    Article  PubMed  CAS  Google Scholar 

  307. Scullard, G.B., Pollard, R.B., Smith, J.L., Sacks, S.L., Gregor, P.B., Robinson, W.S. and Merigan, T.C.: J. Inf. Dis. 143, 772–783 (1981).

    Article  CAS  Google Scholar 

  308. Seeger, C. and Mason, W.S.: Micro. and Mol. Biol. Rev. 64, 51–68 (2000).

    CAS  Google Scholar 

  309. Seifer, M., Hamatake, R.K., Colonno, R.J. and Standring, D.N.: Antimicrob. Agents Chemother. 42, 3200–3208 (1998).

    PubMed  CAS  Google Scholar 

  310. Seifer, M., Hamatake, R., Bifano, M. and Standring, D.N.: J. Virol. 72, 2765–2776 (1998).

    PubMed  CAS  Google Scholar 

  311. Seifer, M. and Standring, D.N.: J. Virol. 67, 4513–4520 (1993).

    PubMed  CAS  Google Scholar 

  312. Seigneres, B., Pichoud, C., Ahmed, S.S., Hantz, O., Trepo, C. and Zoulim, F.: J. Inf. Dis. 181, 1221–1233 (2000).

    Article  CAS  Google Scholar 

  313. Sells, M.A., Chen, M.L. and Acs, G.: Proc. Natl. Acad. Sci. USA 84, 1005–1009 (1987).

    Article  CAS  Google Scholar 

  314. Semino-Mora, C., Leon-Monzon, M. and Dalakas, M.C.: Lab. Invest. 76, 487–495 (1997).

    PubMed  CAS  Google Scholar 

  315. Severini, A., Liu, X.Y., Wilson, J.S. and Tyrrell, D.L.: Antimicrob. Agents Chemother. 39, 1430–1435 (1995).

    Article  PubMed  CAS  Google Scholar 

  316. Shaw, T., Amor, P., Civitico, G., Boyd, M. and Locarnini, S.: Antimicrob. Agents Chemother. 38, 719–723 (1994).

    Article  PubMed  CAS  Google Scholar 

  317. Shaw, T., Mok, S.S. and Locarnini, S.A.: Hepatology 24, 996–1002 (1996).

    Article  CAS  Google Scholar 

  318. Shepp, D.H., Dandliker, P.S., DeMiranda, P., Burnette, T.C., Cederberg, D.M., Kirk, L.E. and Meyers, J.D.: Ann. Int. Med. 103, 368–373 (1985).

    PubMed  CAS  Google Scholar 

  319. Sherker, A.H., Hirota, K., Ornata, M. and Okuda, K.: Gastroenterology 91, 818–824 (1986).

    CAS  Google Scholar 

  320. Sherman, M., Chan, R., Kwan, S., Bloomer, J., Bechtold, C., Ingraham, P., Dehertogh, D., and 008 Study Group: Abstracts of the 37th International Conference on Antimicrobial Agents and Chemotherapy, September 28-October 1, 1997. H-32 (1997).

    Google Scholar 

  321. Shimada, N., Hasegawa, S., Harada, T., Tomisawa, T., Fujii, A. and Takita, T.: J. Antibiotics 39, 1623–1625 (1986).

    Article  CAS  Google Scholar 

  322. Shimada, N., Hasegawa, S., Saito, S., Nishikiori, T., Fujii, A. and Takita, T.: J. Antibiotics 40, 1788–1790 (1987).

    Article  CAS  Google Scholar 

  323. Sidwell, R.W., Huffman, J.H., Khare, G.P., Allen, L.B., Witkowski, J.T. and Robins, R.K.:. Science 177, 705–706 (1972).

    CAS  Google Scholar 

  324. Singh, N. and Gayowski, T.: Transplantation. 59, 1629–30 (1995).

    Article  PubMed  CAS  Google Scholar 

  325. Smilkstein, M.J., Gary, M.D., Knapp, M.S., Kenneth, W., Kulig, M.D. and Rumack, M.D.: J. Med. 24, 1557–1562 (1988).

    Google Scholar 

  326. Staschke, K.A. and Colacino, J.M.: J. Virol. 68, 8265–8269 (1994).

    PubMed  CAS  Google Scholar 

  327. Staschke, K.A., Colacino, J.M., Mabry, T.E. and Jones, C.D.: Antiviral Res. 23, 45–61 (1994).

    Article  CAS  Google Scholar 

  328. Staschke, K.A., Richardson, K.K, Mabry, T.E., Baxter, A.J., Scheuring, J.C., Huffman, D.M., Smith, W.C., Richardson, F.C. and Colacino, J.M.: Nucl. Acids Res. 24, 4111–4116 (1996).

    Article  PubMed  CAS  Google Scholar 

  329. Stephenson, M.L. and Zamecnik, P.C.: Proc. Natl. Acad. Sci. USA 75, 285–288 (1978).

    Article  CAS  Google Scholar 

  330. Stevenson, W., Gaffey, M., Ishitani, M., McCullough, C., Dickson, R., Caldwell, S., Lobo, P. and Pruett, T.: Transpl. Proc. 27, 1219–1221 (1995).

    CAS  Google Scholar 

  331. Streeter, D.G., Witkowski, J.T., Khare, G.P., Sidwell, R.W., Bauer, R.J., Robins, R.K. and Simon, L.N.: Proc. Natl. Acad. Sci. USA 70, 1174–1178 (1973).

    Article  CAS  Google Scholar 

  332. Streeter, D.G., Miller, J.P., Robins, R.K. and Simon, L.N.: Ann. NY. Acad. Sci. 284, 201–210 (1977).

    Article  PubMed  CAS  Google Scholar 

  333. Sudo, K., Konno, K., Shigeta, S. and Yokota, T.: Microbiol. Immunol. 40, 153–159 (1996).

    PubMed  CAS  Google Scholar 

  334. Summers, J. and Mason, W.S.: Cell 29, 403–415 (1983).

    Article  Google Scholar 

  335. Sureau, C., Romet-Lemonne, J.L., Mullins, J.I. and Essex, M.: Cell 47, 37–47 (1986).

    CAS  Google Scholar 

  336. Syamasundar, K.V, Singh, B., Thakur, R.S., Husain, A., Kiso, Y. and Hikino, H.: J. Ethnopharmacol. 14, 41–44 (1985).

    Article  PubMed  CAS  Google Scholar 

  337. Sydiskis, R.J., Owen, D.G., Lohr, J.L., Rosier, K.H.A. and Blomster, R.N.: Antimicrob. Agents Chemother. 35, 2463–2466 (1991).

    Article  PubMed  CAS  Google Scholar 

  338. Tam, R.C., Pai, B., Bard, J., Lim, C., Averett, D.R., Phan, U.T. and Milovanovic, T.: J. Hepatol. 30, 376–382 (1999).

    Article  PubMed  CAS  Google Scholar 

  339. Tang, J., Colacino, J.M., Larsen, S.H. and Spitzer, W.: Antiviral Res. 13, 313–326 (1990).

    Article  CAS  Google Scholar 

  340. Tavis, J.E. and Ganem, D.: Proc. Natl. Acad. Sci. USA 90, 4107–4111 (1993).

    Article  CAS  Google Scholar 

  341. Tavis, J.E. and Ganem, D.: J. Virol. 70, 5741–5750 (1996).

    PubMed  CAS  Google Scholar 

  342. Tencza, M.G. and Newbold, J.E.: J. Med. Virol. 51, 6–16 (1997).

    Article  PubMed  CAS  Google Scholar 

  343. Tennant, B.C.: Clinics Liver Dis. 3, 241–266 (1999).

    Article  Google Scholar 

  344. Tennant, B., Jacob, J., Graham, L.A., Peek, S., Korba, B., Gerin, J.L., Witcher, J.W., Boudinot, F.D., Du, J. and Chu, C.K.: Antiviral Res. 34, A52 (1997).

    Google Scholar 

  345. Tennant, B.C., Baldwin, B.H., Graham, L.A., Ascenzi, M.A., Hornbuckle, W.E., Rowland, P.H., Tochkov, I.A., Yeager, A.E., Erb, H.N., Colacino, J.M. et al.: Hepatol. 28, 179–191 (1998).

    Article  CAS  Google Scholar 

  346. Thomas, D.L., Factor, S.H., Kelen, G.D., Washington, A.S., Taylor, E. Jr. and Quinn, T.C.: Arch. Int. Med. 153, 1705–1712 (1993).

    Article  CAS  Google Scholar 

  347. Thyagarajan, S.P., Thiruneelakantan, K., Subramanian, S. and Sundaravelu, T.: Ind. J. Med. Res. Supplement 76, 124–130 (1982).

    Google Scholar 

  348. Thyagarajan, S.P., Subramanian, S., Thirunalasundari, T., Venkateswaran, P.S., Blumberg, B.S.: Lancet 2, 764–766 (1988).

    Article  PubMed  CAS  Google Scholar 

  349. Tillman, H.L., Troutwein, C., Kruger, M., Boker, K., Schlitt H.J., Condreay, L., Deslauriars, M., Bruns, I., Pichlmayr, R. and Manns, M.P.: J. Hepatology 26 (Suppl. 1), 153 (1997).

    Google Scholar 

  350. Tiollais, P., Pourcel, C. and Dejean, A.: Nature 317, 489–495 (1985).

    Article  PubMed  CAS  Google Scholar 

  351. Tipples, G.A., Ma, M.M., Fischer, K.P, Bain, V.G., Kneteman, N.M. and Tyrrell, D.L.: Hepatology 24, 714–717 (1996).

    CAS  Google Scholar 

  352. Toh, H., Hayashida, H. and Miyata, T.: Nature 305, 827–829 (1983).

    Article  CAS  Google Scholar 

  353. Tong, S., Li, J. and Wands, J.R.: J. Virol. 73, 8696–8702 (1999).

    PubMed  CAS  Google Scholar 

  354. Torresi, J. and Locarnini, S.: Gastroenterol. 118, S83 - S103 (2000).

    Article  CAS  Google Scholar 

  355. Tsiquaye, K.N, Collins, P. and Zuckerman, A.J.: J. Antimicrob. Chemother. 18, 223–228 (1986).

    PubMed  CAS  Google Scholar 

  356. Tsiquaye, K.N, Slomka, M.J. and Maung, M.: J. Med. Virol. 42, 306–310 (1994).

    Article  PubMed  CAS  Google Scholar 

  357. Tsurimoto, T., Fujiyama, A. and Matsubara, K.: Proc. Natl. Acad. Sci. USA 84, 444–448 (1987).

    Article  CAS  Google Scholar 

  358. Tuttleman, J.S., Pugh, J.C. and Summers, J.W.: J. Virol. 58, 17–25 (1986).

    PubMed  CAS  Google Scholar 

  359. Tyrrell, D.L., Fischer, K., Savani, K., Tan, W. and Jewell, L.: Clin. Invest. Med. 16 (Suppl. 4), B77 (1993).

    Google Scholar 

  360. Tyrrell, D.L.J., Mitchell, M.C., de Man, R.A., Schalm, S.W., Main, J., Thomas, H.C. et al.: J. Hepatology 18, 112A (1993).

    Google Scholar 

  361. Ueda, K., Tsurimoto, T., Nagahata, T., Chisaka, O. and Matsubara, K.: Virology 169, 213–316 (1989).

    Article  CAS  Google Scholar 

  362. Van Draanen, N.A., Tisdale, M., Parry, N.R, Jansen, R., Dornsife, R.E., Tuttle, J.V., Averett, D.R. and Koszalka, G.W.: Antimicrob. Agents Chemother. 38, 868–871 (1994).

    Article  PubMed  Google Scholar 

  363. Venkateswaran, P.S., Millman, I. and Blumberg, B.S.: Proc. Natl. Acad. Sci. USA 84, 274–278 (1987).

    Article  CAS  Google Scholar 

  364. von Weizsacker, E, Blum, H.E. and Wands, J.R.: Biophys. Res. Commun. 189, 743–748 (1992).

    Article  CAS  Google Scholar 

  365. von Weizsacker, F., Wieland, S. and Blum, H.E.: Hepatology 24, 294–299 (1996).

    CAS  Google Scholar 

  366. Walters, K., Tipples, G., Allen, M.I. et al.: Hepatology 28 (4 Pt 2), 589A, Abst. No. 1706 (1998).

    Google Scholar 

  367. Wang, G.H. and Seeger, C.: Cell 71, 663–670 (1992).

    Article  PubMed  CAS  Google Scholar 

  368. Wang, G.H. and Seeger, C.: J. Virol. 67, 6507–6512 (1993).

    PubMed  CAS  Google Scholar 

  369. Wang, Y., Bowden, S., Shaw, T., Civitico, G., Chan, Y., Qiao, M. and Locarnini, S.: Antiviral Chem. Chemother. 2, 107–114 (1991).

    CAS  Google Scholar 

  370. Wang, Y., Luscombe, C., Bowden, S., Shaw, T. and Locarnini, S.: Antimicrob. Agents Chemother. 39, 556–558 (1995).

    Article  PubMed  CAS  Google Scholar 

  371. Weber, M., Bronsema, V., Bartos, H., Bosserhoff, A., Bartenschlager, R., and Schaller, H.: J. Virol. 68, 2994–2999 (1994).

    PubMed  CAS  Google Scholar 

  372. Weiss, L., Hildt, E., Hofschneider, P.H.: Antiviral Res. 32, 43–53 (1996).

    Article  PubMed  CAS  Google Scholar 

  373. Welch, P.J., Tritz, R., Yei, S., Barber, J. and Yu, M.: Gene Ther. 4, 736–743 (1997).

    Article  CAS  Google Scholar 

  374. Weller, I.V.D., Bassendine, M.F., Craxi, A., Fowler, M.J.F., Monjardino, J., Thomas, H.C. and Sherlock, S.: Gut 23, 717–723 (1982).

    Article  PubMed  CAS  Google Scholar 

  375. Willis, R.C., Carson, D.A. and Seegmiller, J.E.: Proc. Natl. Acad. Sci. USA 75, 3042–3044 (1978).

    Article  CAS  Google Scholar 

  376. Witcher, J.W., Boudinot, F.D., Baldwin, B.H., Ascenzi, M.A., Tennant, B.C., Du, J.F. and Chu, C.K.: Antimicrob. Agents Chemother. 41, 2184–2187 (1997).

    PubMed  CAS  Google Scholar 

  377. Wolters, L.M., Honkoop, P., Niesters, H.G. and de Man, R.A.: J. Hepatol. 28, 909–910 (1998).

    Article  PubMed  CAS  Google Scholar 

  378. Woo, M.H. and Burnakis, T.G.: Ann. Pharmacother. 31, 330–337 (1997).

    PubMed  CAS  Google Scholar 

  379. Wood, R.C., MacDonald, K.L., White, K.E., Hedberg, C.W., Hanson, M. and Osterholm, M.T.: J. Am. Med. Assoc. 270, 2935–2939 (1993).

    Article  CAS  Google Scholar 

  380. Wright, J.D., Ma, T., Chu, C.K. and Boudinot, F.D.: Pharm. Res. 12, 1350–1353 (1995).

    Article  PubMed  CAS  Google Scholar 

  381. Wright, J.D., Ma, T., Chu, C.K. and Boudinot, F.D.: Drug. Disp. 17, 197–207 (1996).

    Article  CAS  Google Scholar 

  382. Wu, G.Y. and Wu, C.H.: J. Biol. Chem. 267, 12436–12439 (1992).

    PubMed  CAS  Google Scholar 

  383. Xiong, X., Flores, C., Yang, H., Toole, J.J. and Gibbs, C.S.: Hepatology 28, 1669–1673 (1998).

    Article  CAS  Google Scholar 

  384. Yaginuma, K., Shirakata, Y., Kobayashi, M. and Koike, K.: Proc. Natl. Acad. Sci. USA 84, 2678–2682 (1987).

    Article  CAS  Google Scholar 

  385. Yamanaka, G., Wilson, T., Innaimo, S., Bisacchi, G.S., Egli, P., Rinehart, J.K., Zahler, R. and Colonno, R.J.: Antimicrob. Agents Chemother. 43, 190–193 (1999).

    PubMed  CAS  Google Scholar 

  386. Yao, E. and Gish, R.G.: Curr. Gastroenterol. Rep. 1, 20–26 (1999).

    Article  CAS  Google Scholar 

  387. Yao, G.Q., Liu, S.H., Chou, E., Kukhanova, M., Chu, C.K. and Cheng, Y.C.: Biochem. Pharm. 51, 941–947 (1996).

    Article  PubMed  CAS  Google Scholar 

  388. Ying, C., De Clercq, E., Nicholson, W., Furman, P. and Neyts, J.: J. Viral Hepat. 7, 161–165 (2000).

    Article  PubMed  CAS  Google Scholar 

  389. Yokota, T., Mochizuki, S., Konno, K., Mori, S., Shigeta, S. and De Clercq, E.: Antimicrob. Agents Chemother. 35, 394–397 (1991).

    Article  PubMed  CAS  Google Scholar 

  390. Yu, W., Hongsong, C., Fengshui, W., Qianhong, L., Guanghui, C. and Baifang, F.: Chinese Med. J. 109, 674–679 (1996).

    Google Scholar 

  391. Yuen, G.J., Morris, D.M., Mydlow, P.K., Haidar, S., Hall S.T. and Hussey, E.K.: J. Clin. Pharm. 35, 1174–1180 (1995).

    CAS  Google Scholar 

  392. Zahm, F.E., d’Urso, N., Bonino, F. and Ponzetto, A.: Liver 16, 88–93 (1996).

    Article  PubMed  CAS  Google Scholar 

  393. Zamecnik, P.C. and Stephenson, M.L.: Proc. Natl. Acad. Sci. USA 75, 280–284 (1978).

    Article  CAS  Google Scholar 

  394. Zhu, Y.L., Pai, S.B., Liu, S.H., Grove, K.L., Jones, B.C.N.M., Simmons, C., Zemlicka, J. and Cheng, Y.C.: Antimicrob. Agents Chemother. 41, 1755–1760 (1997).

    PubMed  CAS  Google Scholar 

  395. Zoulim, F. and Seeger, C.: J. Virol. 68, 6–13 (1994).

    PubMed  CAS  Google Scholar 

  396. Zoulim, E, Saputelli, J. and Seeger, C.: J. Virol. 68, 2026–2030 (1994).

    PubMed  CAS  Google Scholar 

  397. Zoulim, F., Dannaoui, E., Borel, C., Hantz, O., Lin, T.S., Liu, S.H., Trepo, C. and Cheng, Y.C.: Antimicrob. Agents Chemother. 40, 448–453 (1996).

    PubMed  CAS  Google Scholar 

  398. Zuckerman, A.J.: J. Virol. Methods 17, 119–126 (1987).

    Article  PubMed  CAS  Google Scholar 

  399. zu Putlitz, J., Yu, Q., Burke, J.M. and Wands, J.R.: J. Virol. 73, 5381–5387 (1999).

    PubMed  CAS  Google Scholar 

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    Kirk A. Staschke & Joseph M. Colacino

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Staschke, K.A., Colacino, J.M. (2001). Drug discovery and development of antiviral agents for the treatment of chronic hepatitis B virus infection. In: Jucker, E. (eds) Antiviral Agents. Progress in Drug Research, vol 500. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-7784-8_4

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