N-chlorotaurine is an effective antiviral agent against adenovirus in vitro and in the Ad5/NZW rabbit ocular model.
OBJECTIVE
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.
Romanowski
Eric G
EG
The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. romanowskieg@upmc.edu
Yates
Kathleen A
KA
Teuchner
Barbara
B
Nagl
Markus
M
Irschick
Eveline U
EU
Gordon
Y Jerold
YJ
D000256:Adenoviridae / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D000257:Adenoviridae Infections / Q000517:prevention & control* / Q000821:virology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003315:Cornea / Q000821:virology; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015828:Eye Infections, Viral / Q000517:prevention & control* / Q000821:virology; D005260:Female; D007634:Keratitis / Q000517:prevention & control* / Q000821:virology; D009883:Ophthalmic Solutions / Q000494:pharmacology; D063065:Organophosphonates / Q000494:pharmacology; D011817:Rabbits; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D013654:Taurine; C043410:N-chlorotaurine; D003596:Cytosine; D000077404:Cidofovir