Preclinical evaluation of docusate as protective agent from herpes simplex viruses.
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.
Gong
Y
Y
Viridae Clinical Sciences, Inc., 1134 Burrard Street, Vancouver, British Columbia, V6Z 1Y8, Canada. gongyh@viridae.com
Wen
A
A
Cheung
D
D
Wong
M
M
Sacks
S L
SL
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
D020011:Protective Agents; D013501:Surface-Active Agents; D004143:Dioctyl Sulfosuccinic Acid; D012967:Sodium Dodecyl Sulfate