Candidate sulfonated and sulfated topical microbicides: Comparison of anti-human immunodeficiency virus activities and mechanisms of action

Irini A. Scordi-Bello, Arevik Mosoian, Cejiang He, Yiban Chen, Yang Cheng, Gary A. Jarvis, Maria J. Keller, Kathleen Hogarty, Donald P. Waller, Albert T. Profy, Betsy C. Herold, Mary E. Klotman

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

Poly(styrene 4-sulfonate), cellulose sulfate, polymethylenehydroquinone, and PRO 2000 are sulfated or sulfonated polymers (SPs) under development as topical microbicides. They are presumed to work through similar mechanisms of action, although to date there has been no extensive comparison of their anti-human immunodeficiency virus activities. To determine whether any of these candidate microbicides offers a potential advantage, their in vitro activities, mechanisms of action, stabilities in biological secretions, and toxicities were compared. All four compounds were found to be active against X4, R5, and dualtropic primary isolates and against X4 and R5 laboratory-adapted strains in CD4+ T cells, macrophages, and single-coreceptor cell lines. Our single-cycle experiments using pseudotyped virus suggest that all four SPs function at the binding and entry stages of the viral life cycle but differ in degree of postentry effect. Surface plasmon resonance analyses demonstrate that SPs bind to X4 and R5 monomeric glycoprotein 120 with similar high binding affinities. When mixed with cervicovaginal lavage fluid, SPs maintain inhibitory activity at concentrations achievable in formulations.

Original languageEnglish (US)
Pages (from-to)3607-3615
Number of pages9
JournalAntimicrobial agents and chemotherapy
Volume49
Issue number9
DOIs
StatePublished - Sep 1 2005

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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