Preclinical evaluation of docusate as protective agent from herpes simplexviruses

Prevention of sexually transmitted infections (STIs) is key to public healt h efforts to control these diseases. An effective vaginal microbicide could provide topical, broad-spectrum prevention against the transmission of sev eral STI pathogens. Docusate is a sulfated surfactant and, as such, may ina ctivate viral pathogens by disrupting viral envelopes and/or denaturing/dis associating proteins. Accordingly, the in vitro efficacy and toxicity of do cusate (dioctyl sodium sulfosuccinate Zorex(TM); Meditech Pharmaceuticals, Inc., Scottsdale, Arizona) against herpes simplex viruses (HSV) were evalua ted. Docusate was effective in vitro against wild type and drug-resistant s trains 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 C C50 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 freq uency of use. Kinetics of inactivation examined by pre-mixing virus and dru g in a time-course experiment demonstrated that docusate could reach its EC 90-100 within 30 min. Docusate pretreatment of cells was associated with a 45% reduction in infectivity of those cells, despite a triple washing proce dure. Once infected, an approximate 30%, plaque reduction was observed with treatment. (C) 2001 Elsevier Science B.V. All rights reserved.