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Antimicrobial Agents and Chemotherapy, September 2000, p. 2471-2474, Vol. 44, No. 9
Division of Infectious Diseases, Children's
Hospital Medical Center, Cincinnati, Ohio
45229-3039,1 Department of Pediatrics,
University of Alabama School of Medicine, Birmingham, Alabama
35294,2 and Biomolecular Research
Institute, Clayton 3186, Victoria, Australia3
Received 16 February 2000/Returned for modification 23 May
2000/Accepted 22 June 2000
Dendrimers are large highly branched macromolecules synthesized
from a polyfunctional core. They have shown a variety of biological properties, including, in some instances, antiviral activity. In this
study, five dendrimers were evaluated for in vitro activity against
herpes simplex virus (HSV) types 1 and 2 by cytopathic effect (CPE)
inhibition and plaque reduction (PR) assay in human foreskin fibroblast
cells. All of the compounds were active against both virus types in the
CPE inhibition assay, in which drug was added to the cells prior to the
addition of virus. Antiviral activity was reduced or lost in the PR
assays, in which the cells were incubated with the virus before the
drug was added. The prophylactic efficacy suggested that the dendrimers
might have potential as topical microbicides, products intended to be
applied to the vaginal or rectal mucosa to protect against sexually
transmitted infections. Three dendrimers were evaluated for this
application against genital HSV infection in mice. Two of the
compounds, BRI-2999 and BRI-6741, significantly reduced infection rates
when 15 µl of a 100-mg/ml solution was administered immediately prior
to intravaginal challenge, and the most effective compound, BRI-2999,
provided significant protection even when applied 30 min before
challenge. This is the first report of microbicidal activity by
dendrimers in vivo.
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Dendrimers, a New Class of Candidate Topical
Microbicides with Activity against Herpes Simplex Virus
Infection
*
Corresponding author. Mailing address: Children's
Hospital Medical Center, Division of Infectious Diseases, 3333 Burnet
Ave., Cincinnati, OH 45229. Phone: (513) 636-7666. Fax: (513) 636-7655. E-mail: bourn0{at}chmcc.org.
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