title: Preclinical evaluation of docusate as protective agent from herpes simplex viruses.
abstract: 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; 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 EC(90-100) (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 CC(50) approximately 0.01% vs. SDS approximately 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 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 procedure. Once infected, an approximate 30% plaque reduction was observed with treatment.
authors.affiliation: Viridae Clinical Sciences, Inc., 1134 Burrard Street, Vancouver, British Columbia, V6Z 1Y8, Canada. gongyh@viridae.com
authors.forename: Y
authors.initials: Y
authors.lastname: Gong
authors.forename: A
authors.initials: A
authors.lastname: Wen
authors.forename: D
authors.initials: D
authors.lastname: Cheung
authors.forename: M
authors.initials: M
authors.lastname: Wong
authors.forename: S L
authors.initials: SL
authors.lastname: Sacks
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004143:Dioctyl Sulfosuccinic Acid / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000254:growth & development; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000254:growth & development; D007700:Kinetics; D020011:Protective Agents / Q000494:pharmacology / Q000633:toxicity; D015229:Sexually Transmitted Diseases, Viral / Q000517:prevention & control; D018139:Simplexvirus / Q000187:drug effects*; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology* / Q000633:toxicity; D013501:Surface-Active Agents / Q000494:pharmacology / Q000633:toxicity; D013997:Time Factors; D014709:Vero Cells; D010948:Viral Plaque Assay; D017735:Virus Latency / Q000187:drug effects
chemical_list: D020011:Protective Agents; D013501:Surface-Active Agents; D004143:Dioctyl Sulfosuccinic Acid; D012967:Sodium Dodecyl Sulfate