Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1991 Dec;35(12):2636–2638. doi: 10.1128/aac.35.12.2636

The ability of suramin to block CD4-gp120 binding is reversed in the presence of albumin.

X J Yao 1, M A Wainberg 1, M Richard 1, M Pollak 1
PMCID: PMC245445  PMID: 1810199

Abstract

We have shown that suramin can directly inhibit the binding of the human immunodeficiency virus type 1 gp120 envelope protein to immobilized CD4, thus helping to explain the previously described antiviral properties of suramin. However, physiological concentrations of serum albumin significantly attenuated suramin's antiviral effects, suggesting that only free suramin has antiviral properties. Reported discrepancies between in vitro and clinical activities of suramin may be due to differences between free suramin levels in experimental assays and those achievable clinically.

Full text

PDF
2636

Selected References

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

  1. Baba M., Pauwels R., Balzarini J., Arnout J., Desmyter J., De Clercq E. Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6132–6136. doi: 10.1073/pnas.85.16.6132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Betsholtz C., Johnsson A., Heldin C. H., Westermark B. Efficient reversion of simian sarcoma virus-transformation and inhibition of growth factor-induced mitogenesis by suramin. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6440–6444. doi: 10.1073/pnas.83.17.6440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Broder S., Yarchoan R., Collins J. M., Lane H. C., Markham P. D., Klecker R. W., Redfield R. R., Mitsuya H., Hoth D. F., Gelmann E. Effects of suramin on HTLV-III/LAV infection presenting as Kaposi's sarcoma or AIDS-related complex: clinical pharmacology and suppression of virus replication in vivo. Lancet. 1985 Sep 21;2(8456):627–630. doi: 10.1016/s0140-6736(85)90002-9. [DOI] [PubMed] [Google Scholar]
  4. Cheson B. D., Levine A. M., Mildvan D., Kaplan L. D., Wolfe P., Rios A., Groopman J. E., Gill P., Volberding P. A., Poiesz B. J. Suramin therapy in AIDS and related disorders. Report of the US Suramin Working Group. JAMA. 1987 Sep 11;258(10):1347–1351. [PubMed] [Google Scholar]
  5. Collins J. M., Klecker R. W., Jr, Yarchoan R., Lane H. C., Fauci A. S., Redfield R. R., Broder S., Myers C. E. Clinical pharmacokinetics of suramin in patients with HTLV-III/LAV infection. J Clin Pharmacol. 1986 Jan;26(1):22–26. doi: 10.1002/j.1552-4604.1986.tb02897.x. [DOI] [PubMed] [Google Scholar]
  6. Harada S., Koyanagi Y., Yamamoto N. Infection of HTLV-III/LAV in HTLV-I-carrying cells MT-2 and MT-4 and application in a plaque assay. Science. 1985 Aug 9;229(4713):563–566. doi: 10.1126/science.2992081. [DOI] [PubMed] [Google Scholar]
  7. Lee M. H., Sano K., Morales F. E., Imagawa D. T. Sensitive reverse transcriptase assay to detect and quantitate human immunodeficiency virus. J Clin Microbiol. 1987 Sep;25(9):1717–1721. doi: 10.1128/jcm.25.9.1717-1721.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Levine A. M., Gill P. S., Cohen J., Hawkins J. G., Formenti S. C., Aguilar S., Meyer P. R., Krailo M., Parker J., Rasheed S. Suramin antiviral therapy in the acquired immunodeficiency syndrome. Clinical, immunological, and virologic results. Ann Intern Med. 1986 Jul;105(1):32–37. doi: 10.7326/0003-4819-105-1-32. [DOI] [PubMed] [Google Scholar]
  9. Meijer D. K., van der Sluijs P. Covalent and noncovalent protein binding of drugs: implications for hepatic clearance, storage, and cell-specific drug delivery. Pharm Res. 1989 Feb;6(2):105–118. doi: 10.1023/a:1015961424122. [DOI] [PubMed] [Google Scholar]
  10. Mitsuya H., Looney D. J., Kuno S., Ueno R., Wong-Staal F., Broder S. Dextran sulfate suppression of viruses in the HIV family: inhibition of virion binding to CD4+ cells. Science. 1988 Apr 29;240(4852):646–649. doi: 10.1126/science.2452480. [DOI] [PubMed] [Google Scholar]
  11. Mitsuya H., Popovic M., Yarchoan R., Matsushita S., Gallo R. C., Broder S. Suramin protection of T cells in vitro against infectivity and cytopathic effect of HTLV-III. Science. 1984 Oct 12;226(4671):172–174. doi: 10.1126/science.6091268. [DOI] [PubMed] [Google Scholar]
  12. Müller W. E., Wollert U. Spectroscopic studies on the complex formation of suramin with bovine and human serum albumin. Biochim Biophys Acta. 1976 Apr 14;427(2):465–480. doi: 10.1016/0005-2795(76)90189-6. [DOI] [PubMed] [Google Scholar]
  13. Pollak M., Richard M. Suramin blockade of insulinlike growth factor I-stimulated proliferation of human osteosarcoma cells. J Natl Cancer Inst. 1990 Aug 15;82(16):1349–1352. doi: 10.1093/jnci/82.16.1349. [DOI] [PubMed] [Google Scholar]
  14. Rooke R., Parniak M. A., Tremblay M., Soudeyns H., Li X. G., Gao Q., Yao X. J., Wainberg M. A. Biological comparison of wild-type and zidovudine-resistant isolates of human immunodeficiency virus type 1 from the same subjects: susceptibility and resistance to other drugs. Antimicrob Agents Chemother. 1991 May;35(5):988–991. doi: 10.1128/aac.35.5.988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Schols D., Pauwels R., Desmyter J., De Clercq E. Dextran sulfate and other polyanionic anti-HIV compounds specifically interact with the viral gp120 glycoprotein expressed by T-cells persistently infected with HIV-1. Virology. 1990 Apr;175(2):556–561. doi: 10.1016/0042-6822(90)90440-3. [DOI] [PubMed] [Google Scholar]

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

RESOURCES