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. 1996 Feb;40(2):520–523. doi: 10.1128/aac.40.2.520

(-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (524W91) inhibits hepatitis B virus replication in primary human hepatocytes.

L D Condreay 1, J P Condreay 1, R W Jansen 1, M T Paff 1, D R Averett 1
PMCID: PMC163151  PMID: 8834915

Abstract

The anti-hepatitis B virus (HBV) activity of (-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (524W91) in cultures of primary human hepatocytes was examined. 524W91 was anabolized to the active 5'-triphosphate in these cells. HBV replication was equally inhibited in cultures incubated with 524W91 when the drug was added 24 h preinfection, at infection, or 24 h postinfection. 524W91 inhibited HBV replication by 50% at less than 20 nM in human hepatocytes.

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Selected References

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  1. 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. Evaluation of the potent anti-hepatitis B virus agent (-) cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine in a novel in vivo model. Antimicrob Agents Chemother. 1994 Mar;38(3):616–619. doi: 10.1128/aac.38.3.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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. The anti-hepatitis B virus activities, cytotoxicities, and anabolic profiles of the (-) and (+) enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. Antimicrob Agents Chemother. 1992 Dec;36(12):2686–2692. doi: 10.1128/aac.36.12.2686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gripon P., Diot C., Guguen-Guillouzo C. Reproducible high level infection of cultured adult human hepatocytes by hepatitis B virus: effect of polyethylene glycol on adsorption and penetration. Virology. 1993 Feb;192(2):534–540. doi: 10.1006/viro.1993.1069. [DOI] [PubMed] [Google Scholar]
  4. Ho H. T., Hitchcock M. J. Cellular pharmacology of 2',3'-dideoxy-2',3'-didehydrothymidine, a nucleoside analog active against human immunodeficiency virus. Antimicrob Agents Chemother. 1989 Jun;33(6):844–849. doi: 10.1128/aac.33.6.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Jansen R. W., Johnson L. C., Averett D. R. High-capacity in vitro assessment of anti-hepatitis B virus compound selectivity by a virion-specific polymerase chain reaction assay. Antimicrob Agents Chemother. 1993 Mar;37(3):441–447. doi: 10.1128/aac.37.3.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Korba B. E., Gerin J. L. Use of a standardized cell culture assay to assess activities of nucleoside analogs against hepatitis B virus replication. Antiviral Res. 1992 Jul 1;19(1):55–70. doi: 10.1016/0166-3542(92)90056-b. [DOI] [PubMed] [Google Scholar]
  7. Kreamer B. L., Staecker J. L., Sawada N., Sattler G. L., Hsia M. T., Pitot H. C. Use of a low-speed, iso-density percoll centrifugation method to increase the viability of isolated rat hepatocyte preparations. In Vitro Cell Dev Biol. 1986 Apr;22(4):201–211. doi: 10.1007/BF02623304. [DOI] [PubMed] [Google Scholar]
  8. Lanford R. E., Carey K. D., Estlack L. E., Smith G. C., Hay R. V. Analysis of plasma protein and lipoprotein synthesis in long-term primary cultures of baboon hepatocytes maintained in serum-free medium. In Vitro Cell Dev Biol. 1989 Feb;25(2):174–182. doi: 10.1007/BF02626175. [DOI] [PubMed] [Google Scholar]
  9. Ochiya T., Tsurimoto T., Ueda K., Okubo K., Shiozawa M., Matsubara K. An in vitro system for infection with hepatitis B virus that uses primary human fetal hepatocytes. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1875–1879. doi: 10.1073/pnas.86.6.1875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Sells M. A., Chen M. L., Acs G. Production of hepatitis B virus particles in Hep G2 cells transfected with cloned hepatitis B virus DNA. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1005–1009. doi: 10.1073/pnas.84.4.1005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sells M. A., Zelent A. Z., Shvartsman M., Acs G. Replicative intermediates of hepatitis B virus in HepG2 cells that produce infectious virions. J Virol. 1988 Aug;62(8):2836–2844. doi: 10.1128/jvi.62.8.2836-2844.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Starnes M. C., Cheng Y. C. Cellular metabolism of 2',3'-dideoxycytidine, a compound active against human immunodeficiency virus in vitro. J Biol Chem. 1987 Jan 25;262(3):988–991. [PubMed] [Google Scholar]
  13. Strom S. C., Jirtle R. L., Jones R. S., Novicki D. L., Rosenberg M. R., Novotny A., Irons G., McLain J. R., Michalopoulos G. Isolation, culture, and transplantation of human hepatocytes. J Natl Cancer Inst. 1982 May;68(5):771–778. [PubMed] [Google Scholar]
  14. Tsurimoto T., Fujiyama A., Matsubara K. Stable expression and replication of hepatitis B virus genome in an integrated state in a human hepatoma cell line transfected with the cloned viral DNA. Proc Natl Acad Sci U S A. 1987 Jan;84(2):444–448. doi: 10.1073/pnas.84.2.444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ueda K., Tsurimoto T., Nagahata T., Chisaka O., Matsubara K. An in vitro system for screening anti-hepatitis B virus drugs. Virology. 1989 Mar;169(1):213–216. doi: 10.1016/0042-6822(89)90057-3. [DOI] [PubMed] [Google Scholar]

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