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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Scordi-Bello, IA; Mosoian, A; He, C; Chen, Y; Cheng, Y; Jarvis, GA; Keller, MJ; Hogarty, K; Waller, DP; Profy, AT; Herold, BC; Klotman, ME

Published Date

  • September 2005

Published In

Volume / Issue

  • 49 / 9

Start / End Page

  • 3607 - 3615

PubMed ID

  • 16127029

International Standard Serial Number (ISSN)

  • 0066-4804

Digital Object Identifier (DOI)

  • 10.1128/AAC.49.9.3607-3615.2005

Language

  • eng

Conference Location

  • United States