Related Experiment Videos
Candidate topical microbicides bind herpes simplex virus glycoprotein B and prevent viral entry and cell-to-cell
Natalia Cheshenko1, Marla J Keller, Veronica MasCasullo
1Department of Pediatrics, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1657, New York, NY 10029, USA.
Antimicrobial Agents and Chemotherapy
|May 25, 2004
Summary
New topical microbicides, including PRO 2000, effectively inhibit herpes simplex virus (HSV) infection by blocking viral entry. These sulfated polymers show promise for preventing sexually transmitted infections with minimal impact on cell viability.
Area of Science:
- Virology
- Microbiology
- Drug Discovery
Background:
- Topical microbicides are crucial for preventing sexually transmitted infections (STIs).
- Nonoxynol-9, a current spermicide, may increase human immunodeficiency virus (HIV) transmission risk.
- Heparan sulfate binding by HSV and HIV informed the development of sulfated polymers.
Observation:
- Herpes simplex virus (HSV) and HIV bind to heparan sulfate on host cells.
- Several sulfated polymers, including PRO 2000, polystyrene sulfonate, cellulose sulfate, and polymethylenehydroquinone sulfonate, were investigated for anti-HSV activity.
- The anti-HSV activity spectrum, mechanism, and effects on inflammatory mediators were not fully evaluated.
Findings:
- PRO 2000 and related sulfated polymers demonstrated a 10,000-fold inhibition of HSV infection, including against acyclovir-resistant strains.
- These compounds form stable complexes with viral glycoprotein B, inhibiting viral binding, entry, and cell-to-cell spread.
- Antiviral activity was maintained in cervical secretions and across a wide pH range, with minimal impact on cell viability.
Implications:
- Sulfated polymers represent a promising class of topical microbicides for STI prevention.
- Their stable interaction with viruses suggests long-lasting efficacy.
- Further clinical evaluation is warranted to confirm safety and effectiveness in preventing HSV and HIV acquisition.