Sulfonic acid dyes: Inhibition of the human immunodeficiency virus and mechanism of action

D. J. Clanton, R. A. Moran, J. B. McMahon, O. S. Weislow, R. W. Buckheit, M. G. Hollingshead, V. Ciminale, B. K. Felber, G. N. Pavlakis, J. P. Bader

Research output: Contribution to journalArticle

Abstract

Over 50 different commercially available sulfonic acid-containing dyes were analyzed for their ability to prevent HIV-l-induced cell killing and in inhibiting HIV-1 replication. Compounds of remarkably similar structure, but with differing patterns of sulfonic acid group substitutions, had a wide range of potency in inhibiting HIV-1. Chicago sky blue (CSB) was highly effective in the inhibition of HIV-1 with less toxicity to CEM-SS cells than most of the other sulfonated dyes tested. Synthesis of CSB was undertaken to produce a product greater than 98% pure and this compound was used to elucidate the possible mechanisms by which this class of structurally related compounds inhibits HIV-1. Addition of CSB to cells infected at high multiplicity at any time up to 24 h after infection, unlike dideoxycytidine (ddC) or oxathiin carboxanilide (OC), inhibited HIV-l-induced cell killing. Other postinfection time course studies revealed that CSB had to be present for 24 h or longer immediately after infection to be protective. Virus binding to cells occurred in the presence of CSB, but the requirement for virion envelope-cell membrane fusion was delayed. CSB was a potent inhibitor of the reverse transcriptase (RT) of both HIV-1 and HIV-2, although it was less active against HIV-2 in a cell killing-based assay. CSB also inhibited Rauscher and LP-BM5 murine leukemia viruses. CSB appears to disrupt the interaction between viral proteins and cell membranes, both in the fusion step early in the infection cycle, and in the development of syncytia in the late stages of virus infection.

Original languageEnglish
Pages (from-to)771-781
Number of pages11
JournalJournal of Acquired Immune Deficiency Syndromes
Volume5
Issue number8
Publication statusPublished - 1992

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Keywords

  • Cell killing
  • Chicago sky blue
  • HIV-1
  • Sulfonic acid dyes

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Virology
  • Immunology and Allergy

Cite this

Clanton, D. J., Moran, R. A., McMahon, J. B., Weislow, O. S., Buckheit, R. W., Hollingshead, M. G., Ciminale, V., Felber, B. K., Pavlakis, G. N., & Bader, J. P. (1992). Sulfonic acid dyes: Inhibition of the human immunodeficiency virus and mechanism of action. Journal of Acquired Immune Deficiency Syndromes, 5(8), 771-781.