Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1990 Jun;34(6):1297–1300. doi: 10.1128/aac.34.6.1297

Activities of (-)-carbovir and 3'-azido-3'-deoxythymidine against human immunodeficiency virus in vitro.

S G Carter 1, J A Kessler 1, C D Rankin 1
PMCID: PMC171808  PMID: 2393292

Abstract

(-)-Carbovir, the minus optical isomer of carbocyclic-2',3'-didehydro-2',3'-dideoxyguanosine, has been shown to be the biologically active form for the inhibition of human immunodeficiency virus type 1 replication. The concentration of (-)-carbovir required to reduce reverse transcriptase activity by 50% compared with the control was 0.8 microM in H9 cells infected with the HTLV-IIIb strain; the 50% inhibitory concentration for cytotoxicity was greater than 2 mM in these cells. The effect of the timing of drug addition, pre- and postinfection, and the effect of increasing amounts of virus on the antiviral activities of (-)-carbovir and 3'-azido-3'-deoxythymidine were determined.

Full text

PDF
1297

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahluwalia G., Cooney D. A., Mitsuya H., Fridland A., Flora K. P., Hao Z., Dalal M., Broder S., Johns D. G. Initial studies on the cellular pharmacology of 2',3'-dideoxyinosine, an inhibitor of HIV infectivity. Biochem Pharmacol. 1987 Nov 15;36(22):3797–3800. doi: 10.1016/0006-2952(87)90440-0. [DOI] [PubMed] [Google Scholar]
  2. Alley M. C., Scudiero D. A., Monks A., Hursey M. L., Czerwinski M. J., Fine D. L., Abbott B. J., Mayo J. G., Shoemaker R. H., Boyd M. R. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res. 1988 Feb 1;48(3):589–601. [PubMed] [Google Scholar]
  3. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  4. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  5. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  6. Broder S., Gallo R. C. A pathogenic retrovirus (HTLV-III) linked to AIDS. N Engl J Med. 1984 Nov 15;311(20):1292–1297. doi: 10.1056/NEJM198411153112006. [DOI] [PubMed] [Google Scholar]
  7. Fischl M. A., Richman D. D., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Schooley R. T. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):185–191. doi: 10.1056/NEJM198707233170401. [DOI] [PubMed] [Google Scholar]
  8. Fischl M. A., Richman D. D., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Schooley R. T. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):185–191. doi: 10.1056/NEJM198707233170401. [DOI] [PubMed] [Google Scholar]
  9. Fischl M. A., Richman D. D., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Schooley R. T. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):185–191. doi: 10.1056/NEJM198707233170401. [DOI] [PubMed] [Google Scholar]
  10. Gonda M. A., Braun M. J., Clements J. E., Pyper J. M., Wong-Staal F., Gallo R. C., Gilden R. V. Human T-cell lymphotropic virus type III shares sequence homology with a family of pathogenic lentiviruses. Proc Natl Acad Sci U S A. 1986 Jun;83(11):4007–4011. doi: 10.1073/pnas.83.11.4007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hagler D. N., Frame P. T. Azidothymidine neurotoxicity. Lancet. 1986 Dec 13;2(8520):1392–1393. doi: 10.1016/s0140-6736(86)92029-5. [DOI] [PubMed] [Google Scholar]
  12. Lin T. S., Schinazi R. F., Prusoff W. H. Potent and selective in vitro activity of 3'-deoxythymidin-2'-ene (3'-deoxy-2',3'-didehydrothymidine) against human immunodeficiency virus. Biochem Pharmacol. 1987 Sep 1;36(17):2713–2718. doi: 10.1016/0006-2952(87)90253-x. [DOI] [PubMed] [Google Scholar]
  13. Mitsuya H., Broder S. Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by 2',3'-dideoxynucleosides. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1911–1915. doi: 10.1073/pnas.83.6.1911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Murray J. F., Felton C. P., Garay S. M., Gottlieb M. S., Hopewell P. C., Stover D. E., Teirstein A. S. Pulmonary complications of the acquired immunodeficiency syndrome. Report of a National Heart, Lung, and Blood Institute workshop. N Engl J Med. 1984 Jun 21;310(25):1682–1688. doi: 10.1056/NEJM198406213102529. [DOI] [PubMed] [Google Scholar]
  15. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Richman D. D., Fischl M. A., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Hirsch M. S. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):192–197. doi: 10.1056/NEJM198707233170402. [DOI] [PubMed] [Google Scholar]
  17. Richman D. D., Fischl M. A., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Hirsch M. S. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):192–197. doi: 10.1056/NEJM198707233170402. [DOI] [PubMed] [Google Scholar]
  18. Richman D. D., Fischl M. A., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Hirsch M. S. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):192–197. doi: 10.1056/NEJM198707233170402. [DOI] [PubMed] [Google Scholar]
  19. Sommadossi J. P., Carlisle R. Toxicity of 3'-azido-3'-deoxythymidine and 9-(1,3-dihydroxy-2-propoxymethyl)guanine for normal human hematopoietic progenitor cells in vitro. Antimicrob Agents Chemother. 1987 Mar;31(3):452–454. doi: 10.1128/aac.31.3.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sonigo P., Alizon M., Staskus K., Klatzmann D., Cole S., Danos O., Retzel E., Tiollais P., Haase A., Wain-Hobson S. Nucleotide sequence of the visna lentivirus: relationship to the AIDS virus. Cell. 1985 Aug;42(1):369–382. doi: 10.1016/s0092-8674(85)80132-x. [DOI] [PubMed] [Google Scholar]
  21. Spira T. J., Bozeman L. H., Holman R. C., Warfield D. T., Phillips S. K., Feorino P. M. Micromethod for assaying reverse transcriptase of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus. J Clin Microbiol. 1987 Jan;25(1):97–99. doi: 10.1128/jcm.25.1.97-99.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vince R., Hua M., Brownell J., Daluge S., Lee F. C., Shannon W. M., Lavelle G. C., Qualls J., Weislow O. S., Kiser R. Potent and selective activity of a new carbocyclic nucleoside analog (carbovir: NSC 614846) against human immunodeficiency virus in vitro. Biochem Biophys Res Commun. 1988 Oct 31;156(2):1046–1053. doi: 10.1016/s0006-291x(88)80950-1. [DOI] [PubMed] [Google Scholar]
  23. White E. L., Parker W. B., Macy L. J., Shaddix S. C., McCaleb G., Secrist J. A., 3rd, Vince R., Shannon W. M. Comparison of the effect of Carbovir, AZT, and dideoxynucleoside triphosphates on the activity of human immunodeficiency virus reverse transcriptase and selected human polymerases. Biochem Biophys Res Commun. 1989 Jun 15;161(2):393–398. doi: 10.1016/0006-291x(89)92611-9. [DOI] [PubMed] [Google Scholar]
  24. Yarchoan R., Klecker R. W., Weinhold K. J., Markham P. D., Lyerly H. K., Durack D. T., Gelmann E., Lehrman S. N., Blum R. M., Barry D. W. Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet. 1986 Mar 15;1(8481):575–580. doi: 10.1016/s0140-6736(86)92808-4. [DOI] [PubMed] [Google Scholar]
  25. Yarchoan R., Perno C. F., Thomas R. V., Klecker R. W., Allain J. P., Wills R. J., McAtee N., Fischl M. A., Dubinsky R., McNeely M. C. Phase I studies of 2',3'-dideoxycytidine in severe human immunodeficiency virus infection as a single agent and alternating with zidovudine (AZT). Lancet. 1988 Jan 16;1(8577):76–81. doi: 10.1016/s0140-6736(88)90283-8. [DOI] [PubMed] [Google Scholar]
  26. Ziegler J. L., Beckstead J. A., Volberding P. A., Abrams D. I., Levine A. M., Lukes R. J., Gill P. S., Burkes R. L., Meyer P. R., Metroka C. E. Non-Hodgkin's lymphoma in 90 homosexual men. Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome. N Engl J Med. 1984 Aug 30;311(9):565–570. doi: 10.1056/NEJM198408303110904. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES