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 ina...

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Bibliographic Details
Published in:Antiviral research 2001-10, Vol.52 (1), p.25-32
Main Authors: Gong, Yunhao, Wen, Aimin, Cheung, Dorothy, Wong, Michelle, Sacks, Stephen L.
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Biological and medical sciences
Cells, Cultured
Cercopithecus aethiops
Dioctyl Sulfosuccinic Acid - pharmacology
Dioctyl Sulfosuccinic Acid - toxicity
Docusate
Dose-Response Relationship, Drug
Herpes simplex virus
Herpesvirus 1, Human - drug effects
Herpesvirus 1, Human - growth & development
Herpesvirus 2, Human - drug effects
Herpesvirus 2, Human - growth & development
Kinetics
Medical sciences
Pharmacology. Drug treatments
Preclinical evaluation
Protective Agents - pharmacology
Protective Agents - toxicity
Sexually Transmitted Diseases, Viral - prevention & control
Simplexvirus - drug effects
Sodium Dodecyl Sulfate - pharmacology
Sodium Dodecyl Sulfate - toxicity
Surface-Active Agents - pharmacology
Surface-Active Agents - toxicity
Time Factors
Vero Cells
Viral Plaque Assay
Virus Latency - drug effects
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Summary: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 ∼0.01% vs. SDS ∼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.
ISSN:0166-3542
1872-9096
DOI:10.1016/S0166-3542(01)00156-5