Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1995 Apr 1;307(Pt 1):129–134. doi: 10.1042/bj3070129

Anti-(human immunodeficiency virus) activity of polyoxotungstates and their inhibition of human immunodeficiency virus reverse transcriptase.

P S Moore 1, C J Jones 1, N Mahmood 1, I G Evans 1, M Goff 1, R Cooper 1, A J Hay 1
PMCID: PMC1136754  PMID: 7536411

Abstract

Heteropolyoxotungstates of the Keggin class containing different heteroatoms were tested for inhibition of two strains of human immunodeficiency virus 1 (HIV-1); they exhibited varying antiviral activity. Compounds containing boron were inactive, only one of those containing phosphorus showed selective anti-viral activity, whereas all silicon-containing compounds exhibited significant anti-viral activity in C8166 cells infected with the IIIB strain. Their effectiveness was some 10-fold higher in JM cells with selectivity indices of about 2000. The silicotungstates were effective inhibitors of HIV reverse transcriptase, showing greater inhibition with RNA/DNA template primers than with DNA/DNA template.primer. Kinetic analysis demonstrated that they inhibit the enzyme by different mechanisms, as, of the four compounds examined, two competed with template.primer and two competed with deoxynucleoside triphosphate. Inhibition of DNA polymerase activity by these compounds was compared using polymerases from different sources, including human; although not necessarily most specific for HIV-1 reverse transcriptase, they did not inhibit all DNA polymerases to a similar degree.

Full text

PDF
129

Selected References

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

  1. Bonissol C., Kona P., Chermann J. C., Jasmin C., Raynaud M. Action antivirale des polyanions minéraux condensés. Inhibition in vitro du virus de la rubéole. C R Acad Sci Hebd Seances Acad Sci D. 1972 May 29;274(22):3030–3033. [PubMed] [Google Scholar]
  2. Chermann J. C., Sinoussi F. C., Jasmin C. Inhibition of RNA-dependent DNA polymerase of murine oncornaviruses by ammonium-5-tungsto-2-antimoniate. Biochem Biophys Res Commun. 1975 Aug 18;65(4):1229–1236. doi: 10.1016/s0006-291x(75)80361-5. [DOI] [PubMed] [Google Scholar]
  3. Debyser Z., Pauwels R., Andries K., Desmyter J., Kukla M., Janssen P. A., De Clercq E. An antiviral target on reverse transcriptase of human immunodeficiency virus type 1 revealed by tetrahydroimidazo-[4,5,1-jk] [1,4]benzodiazepin-2 (1H)-one and -thione derivatives. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1451–1455. doi: 10.1073/pnas.88.4.1451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hill C. L., Weeks M. S., Schinazi R. F. Anti-HIV-1 activity, toxicity, and stability studies of representative structural families of polyoxometalates. J Med Chem. 1990 Oct;33(10):2767–2772. doi: 10.1021/jm00172a014. [DOI] [PubMed] [Google Scholar]
  5. Jasmin C., Raybaud N., Chermann J. C., Haapala D., Sinoussi F., Loustau C. B., Bonissol C., Kona P., Raynaud M. In vitro effects of silicotungstate on some RNA viruses. Biomedicine. 1973 Jul;18(4):319–327. [PubMed] [Google Scholar]
  6. Kimberlin R. H., Walker C. A. The antiviral compound HPA-23 can prevent scrapie when administered at the time of infection. Arch Virol. 1983;78(1-2):9–18. doi: 10.1007/BF01310854. [DOI] [PubMed] [Google Scholar]
  7. Lightfoote M. M., Coligan J. E., Folks T. M., Fauci A. S., Martin M. A., Venkatesan S. Structural characterization of reverse transcriptase and endonuclease polypeptides of the acquired immunodeficiency syndrome retrovirus. J Virol. 1986 Nov;60(2):771–775. doi: 10.1128/jvi.60.2.771-775.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Majumdar C., Abbotts J., Broder S., Wilson S. H. Studies on the mechanism of human immunodeficiency virus reverse transcriptase. Steady-state kinetics, processivity, and polynucleotide inhibition. J Biol Chem. 1988 Oct 25;263(30):15657–15665. [PubMed] [Google Scholar]
  9. Merluzzi V. J., Hargrave K. D., Labadia M., Grozinger K., Skoog M., Wu J. C., Shih C. K., Eckner K., Hattox S., Adams J. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science. 1990 Dec 7;250(4986):1411–1413. doi: 10.1126/science.1701568. [DOI] [PubMed] [Google Scholar]
  10. Moore P. S., Pizza C. Observations on the inhibition of HIV-1 reverse transcriptase by catechins. Biochem J. 1992 Dec 15;288(Pt 3):717–719. doi: 10.1042/bj2880717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ono K., Nakane H., Fukushima M. Differential inhibition of various deoxyribonucleic and ribonucleic acid polymerases by suramin. Eur J Biochem. 1988 Mar 1;172(2):349–353. doi: 10.1111/j.1432-1033.1988.tb13893.x. [DOI] [PubMed] [Google Scholar]
  12. Pauwels R., Balzarini J., Baba M., Snoeck R., Schols D., Herdewijn P., Desmyter J., De Clercq E. Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. J Virol Methods. 1988 Aug;20(4):309–321. doi: 10.1016/0166-0934(88)90134-6. [DOI] [PubMed] [Google Scholar]
  13. Raynaud M., Chermann J. C., Plata F., Jasmin C., Mathé G. Inhibiteurs des virus de groupe leucémie-sarcome murine. Silicotungstates. C R Acad Sci Hebd Seances Acad Sci D. 1971 Jan 11;272(2):347–348. [PubMed] [Google Scholar]
  14. Rozenbaum W., Dormont D., Spire B., Vilmer E., Gentilini M., Griscelli C., Montagnier L., Barre-Sinoussi F., Chermann J. C. Antimoniotungstate (HPA 23) treatment of three patients with AIDS and one with prodrome. Lancet. 1985 Feb 23;1(8426):450–451. doi: 10.1016/s0140-6736(85)91162-6. [DOI] [PubMed] [Google Scholar]
  15. Take Y., Tokutake Y., Inouye Y., Yoshida T., Yamamoto A., Yamase T., Nakamura S. Inhibition of proliferation of human immunodeficiency virus type 1 by novel heteropolyoxotungstates in vitro. Antiviral Res. 1991 Feb;15(2):113–124. doi: 10.1016/0166-3542(91)90029-q. [DOI] [PubMed] [Google Scholar]
  16. Wu J. C., Warren T. C., Adams J., Proudfoot J., Skiles J., Raghavan P., Perry C., Potocki I., Farina P. R., Grob P. M. A novel dipyridodiazepinone inhibitor of HIV-1 reverse transcriptase acts through a nonsubstrate binding site. Biochemistry. 1991 Feb 26;30(8):2022–2026. doi: 10.1021/bi00222a003. [DOI] [PubMed] [Google Scholar]
  17. di Marzo Veronese F., Copeland T. D., DeVico A. L., Rahman R., Oroszlan S., Gallo R. C., Sarngadharan M. G. Characterization of highly immunogenic p66/p51 as the reverse transcriptase of HTLV-III/LAV. Science. 1986 Mar 14;231(4743):1289–1291. doi: 10.1126/science.2418504. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES