Abstract
The metabolism of acyclovir to its mono-, di-, and triphosphate derivatives was examined in uninfected and virus-infected cells. The level of phosphorylation of acyclovir was dependent upon virus type, cell line, exogenous drug concentration, and exposure time. Acyclovir phosphorylation was inhibited by exogenously added nucleosides. The order of inhibition was deoxythymidine greater than deoxycytidine greater than guanosine greater than or equal to deoxyguanosine. Acyclovir triphosphate persisted in infected cells after removal of the drug from the medium. The initial half-life of the triphosphate was 1.2 h in the absence of the drug in the medium, but triphosphate levels reached a plateau after 6 h. The presence of low concentrations of the drug in the medium resulted in a longer persistence of the intracellular triphosphate and a higher plateau level.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bittlingmaier K., Schneider D., Falke D. Thymidine transport in herpesvirus hominis type 1 and 2 infected BHK 21 cells. J Gen Virol. 1977 Apr;35(1):159–173. doi: 10.1099/0022-1317-35-1-159. [DOI] [PubMed] [Google Scholar]
- Cheng Y. C., Ostrander M. Deoxythymidine kinase induced in HeLa TK- cells by herpes simplex virus type I and type II. II. Purification and characterization. J Biol Chem. 1976 May 10;251(9):2605–2610. [PubMed] [Google Scholar]
- Colby B. M., Furman P. A., Shaw J. E., Elion G. B., Pagano J. S. Phosphorylation of acyclovir [9-(2-hydroxyethoxymethyl)guanine] in Epstein-Barr virus-infected lymphoblastoid cell lines. J Virol. 1981 May;38(2):606–611. doi: 10.1128/jvi.38.2.606-611.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collins P., Bauer D. J. The activity in vitro against herpes virus of 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine), a new antiviral agent. J Antimicrob Chemother. 1979 Jul;5(4):431–436. doi: 10.1093/jac/5.4.431. [DOI] [PubMed] [Google Scholar]
- Datta A. K., Colby B. M., Shaw J. E., Pagano J. S. Acyclovir inhibition of Epstein-Barr virus replication. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5163–5166. doi: 10.1073/pnas.77.9.5163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elion G. B., Furman P. A., Fyfe J. A., de Miranda P., Beauchamp L., Schaeffer H. J. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5716–5720. doi: 10.1073/pnas.74.12.5716. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Estes J. E., Huang E. S. Stimulation of cellular thymidine kinases by human cytomegalovirus. J Virol. 1977 Oct;24(1):13–21. doi: 10.1128/jvi.24.1.13-21.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Furman P. A., McGuirt P. V., Keller P. M., Fyfe J. A., Elion G. B. Inhibition by acyclovir of cell growth and DNA synthesis of cells biochemically transformed with herpesvirus genetic information. Virology. 1980 Apr 30;102(2):420–430. doi: 10.1016/0042-6822(80)90109-9. [DOI] [PubMed] [Google Scholar]
- Furman P. A., St Clair M. H., Fyfe J. A., Rideout J. L., Keller P. M., Elion G. B. Inhibition of herpes simplex virus-induced DNA polymerase activity and viral DNA replication by 9-(2-hydroxyethoxymethyl)guanine and its triphosphate. J Virol. 1979 Oct;32(1):72–77. doi: 10.1128/jvi.32.1.72-77.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fyfe J. A., Keller P. M., Furman P. A., Miller R. L., Elion G. B. Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl)guanine. J Biol Chem. 1978 Dec 25;253(24):8721–8727. [PubMed] [Google Scholar]
- Miller W. H., Miller R. L. Phosphorylation of acyclovir (acycloguanosine) monophosphate by GMP kinase. J Biol Chem. 1980 Aug 10;255(15):7204–7207. [PubMed] [Google Scholar]
- Schaeffer H. J., Beauchamp L., de Miranda P., Elion G. B., Bauer D. J., Collins P. 9-(2-hydroxyethoxymethyl) guanine activity against viruses of the herpes group. Nature. 1978 Apr 13;272(5654):583–585. doi: 10.1038/272583a0. [DOI] [PubMed] [Google Scholar]
- St Clair M. H., Furman P. A., Lubbers C. M., Elion G. B. Inhibition of cellular alpha and virally induced deoxyribonucleic acid polymerases by the triphosphate of acyclovir. Antimicrob Agents Chemother. 1980 Nov;18(5):741–745. doi: 10.1128/aac.18.5.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Miranda P., Whitley R. J., Blum M. R., Keeney R. E., Barton N., Cocchetto D. M., Good S., Hemstreet G. P., 3rd, Kirk L. E., Page D. A. Acyclovir kinetics after intravenous infusion. Clin Pharmacol Ther. 1979 Dec;26(6):718–728. doi: 10.1002/cpt1979266718. [DOI] [PubMed] [Google Scholar]
