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N-氯代牛磺酸在体外以及Ad5/NZW兔眼部模型中是一种有效的抗腺病毒抗病毒剂。

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

作者信息

Romanowski Eric G, Yates Kathleen A, Teuchner Barbara, Nagl Markus, Irschick Eveline U, Gordon Y Jerold

机构信息

The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

出版信息

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.

摘要

目的

确定N - 氯代牛磺酸(NCT)在体外以及在Ad5/NZW兔眼部模型中是否具有抗腺病毒(Ad)的活性。

方法

通过将不同腺病毒血清型与几种浓度的NCT孵育1小时,并测定腺病毒滴度的降低情况,来评估NCT的体外活性。在兔研究1中,用2.5%、2.0%和1.0%的NCT、0.5%的西多福韦或生理盐水治疗感染Ad5的眼睛。NCT组和生理盐水组每天治疗1次,共治疗10天,之后每天治疗5次,持续6天。在兔研究2中,用1.0% NCT/0.1%氯化铵(NH4Cl)、0.1% NCT/1.0% NH4Cl、0.1% NCT/0.1% NH4Cl、0.5%西多福韦或生理盐水治疗感染Ad5的眼睛。NCT组和生理盐水组每天治疗5次,持续10天。接受西多福韦治疗的眼睛采用作者的标准西多福韦给药方案:每天2次,持续7天。

结果

在体外,NCT对所有测试的眼部腺病毒血清型均表现出浓度依赖性的直接灭活作用。兔研究1:在第1至14天,与生理盐水相比,2.5%、2.0%、1.0%的NCT以及西多福韦在总培养物中阳性培养物显著减少。兔研究2:在第1至14天,1.0% NCT/0.1% NH4Cl、0.1% NCT/1.0% NH4Cl、0.1% NCT/0.1% NH4Cl以及西多福韦在总培养物中阳性培养物显著减少;在第7至14天,病毒脱落持续时间更短,平均综合滴度更低。在两项兔研究的多项结果指标中,西多福韦均比NCT显著更有效。

结论

NCT在体外和体内均表现出抗腺病毒活性。表明NCT作为局部抗菌剂有进一步开发的价值。

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