Preclinical evaluation of docusate as protective agent from herpes simplex viruses
Preclinical evaluation of docusate as protective agent from herpes simplex viruses
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DOI：
10.1016/s0166-3542(01)00156-5
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发表时间：
2001-10-01
影响因子：
7.6
通讯作者：
Sacks, SL
中科院分区：
文献类型：
--
作者：
Gong, YH;Wen, AM;Sacks, SL
防止性传播感染(STI)是控制这些疾病的公共卫生努力的关键。一种有效的阴道杀菌剂可以提供局部的、广谱的预防几种STI病原体的传播。Docusate是一种硫酸盐化表面活性剂，因此可以通过破坏病毒包膜和/或变性/解离蛋白来灭活病毒病原体。因此，我们评估了DOCUS(二辛基磺基琥珀酸钠Zorex(TM)；Meditech PharmPharmticals，Inc.，Scottsdale，Arizona)对单纯疱疹病毒(HSV)的体外疗效和毒性。Docusate在体外对1型和2型HSV野生型和耐药株有效，EC90-100(使病毒产量下降90-100%的有效浓度)约为0.005%(w/v)。十二烷基硫酸钠与十二烷基硫酸钠相当，但与十二烷基硫酸钠孵育2天后，对未感染的Vero细胞的毒性略低于十二烷基硫酸钠(十二烷基硫酸钠CC50类似于0.01%，十二烷基硫酸钠类似于十二烷基硫酸钠0.005%)。多糖酯的细胞毒性曲线是时间和剂量依赖的，因此与使用频率有关。用病毒与药物预混的时程实验研究了灭活动力学，结果表明，DOC90-100在30min内即可达到其EC90-100。尽管有三次洗涤程序，但细胞的Docusate预处理与这些细胞的感染性降低45%有关。一旦感染，通过治疗观察到大约30%的斑块减少。(C)2001 Elsevier Science B.V.保留所有权利。
Prevention of sexually transmitted infections (STIs) is key to public health efforts to control these diseases. An effective vaginal microbicide could provide topical, broad-spectrum prevention against the transmission of several STI pathogens. Docusate is a sulfated surfactant and, as such, may inactivate viral pathogens by disrupting viral envelopes and/or denaturing/disassociating proteins. Accordingly, the in vitro efficacy and toxicity of docusate (dioctyl sodium sulfosuccinate Zorex(TM); Meditech Pharmaceuticals, Inc., Scottsdale, Arizona) against herpes simplex viruses (HSV) were evaluated. Docusate was effective in vitro against wild type and drug-resistant strains of HSV type 1 and 2 with EC90-100 (effective concentration giving 90-100% virus yield reduction) of approximately 0.005% (w/v). Sodium dodecyl sulfate (SDS) was equipotent, however, docusate was somewhat less toxic to uninfected Vero cells compared with SDS after 2 days incubation (docusate CC50 similar to 0.01% vs. SDS similar to 0.005%). The cytotoxicity profiles of docusate were time- and dose-dependent and thus associated with the frequency of use. Kinetics of inactivation examined by pre-mixing virus and drug in a time-course experiment demonstrated that docusate could reach its EC90-100 within 30 min. Docusate pretreatment of cells was associated with a 45% reduction in infectivity of those cells, despite a triple washing procedure. Once infected, an approximate 30%, plaque reduction was observed with treatment. (C) 2001 Elsevier Science B.V. All rights reserved.