N-chlorotaurine is an effective antiviral agent against adenovirus in vitro and in the Ad5/NZW rabbit ocular model

Invest Ophthalmol Vis Sci. 2006 May;47(5):2021-6. doi: 10.1167/iovs.05-1270.

Abstract

Purpose: To determine whether N-chlorotaurine (NCT) demonstrates antiviral activity against adenovirus (Ad) in vitro and in the Ad5/NZW rabbit ocular model.

Methods: The in vitro activity of NCT was evaluated by incubating different Ad serotypes with several concentrations of NCT for 1 hour and determining the reduction in Ad titers. In rabbit study 1, Ad5-infected eyes were treated with 2.5%, 2.0%, and 1.0% NCT; 0.5% cidofovir; or saline. NCT and saline groups were treated 10 times for 1 day and then 5 times daily for 6 days. In rabbit study 2, Ad5-infected eyes were treated with 1.0% NCT/0.1% ammonium chloride (NH4Cl), 0.1% NCT/1.0% NH4Cl, 0.1% NCT/0.1% NH4Cl, and 0.5% cidofovir or saline. The NCT and saline groups were treated five times daily for 10 days. Cidofovir-treated eyes received the authors' standard cidofovir dose regimen: twice daily for 7 days.

Results: In vitro, NCT demonstrated concentration-dependent direct inactivation of all ocular Ad serotypes tested. Rabbit study 1: 2.5%, 2.0%, 1.0% NCT, and cidofovir demonstrated significantly fewer positive cultures per total cultures during days 1 to 14, compared with saline. Rabbit study 2: 1.0% NCT/0.1% NH4Cl, 0.1% NCT/1.0% NH4Cl, 0.1% NCT/0.1% NH4Cl, and cidofovir demonstrated significantly fewer positive cultures per total cultures, during days 1 to 14; shorter durations of shedding; and lower mean combined titers, during days 7 to 14, compared with saline. Cidofovir was significantly more effective than NCT in several outcome measures in both rabbit studies.

Conclusions: NCT demonstrated antiviral activity against adenovirus in vitro and in vivo. Further development of NCT as a topical antimicrobial is indicated.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / drug effects*
  • Adenoviridae / growth & development
  • Adenoviridae / isolation & purification
  • Adenoviridae Infections / prevention & control*
  • Adenoviridae Infections / virology
  • Animals
  • Antiviral Agents / pharmacology*
  • Cidofovir
  • Cornea / virology
  • Cytosine / analogs & derivatives
  • Cytosine / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Eye Infections, Viral / prevention & control*
  • Eye Infections, Viral / virology
  • Female
  • Keratitis / prevention & control*
  • Keratitis / virology
  • Ophthalmic Solutions / pharmacology
  • Organophosphonates / pharmacology
  • Rabbits
  • Taurine / analogs & derivatives*
  • Taurine / pharmacology
  • Viral Plaque Assay
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Ophthalmic Solutions
  • Organophosphonates
  • Taurine
  • N-chlorotaurine
  • Cytosine
  • Cidofovir