Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9000865 | Antiviral Research | 2005 | 8 Pages |
Abstract
Dendrimers are a novel class of polyanionic macromolecules with broad-spectrum antiviral activities and minimal toxicities. A new generation of amide dendrimer, SPL7013, was evaluated as a lead microbicide candidate against herpes simplex viruses (HSV). The plaque reduction assays showed that the 50% effective concentrations (EC50) determined by pre-treatment of cells were 2.0 μg/ml for HSV-1 and 0.5 μg/ml for HSV-2. Inhibitory effects were also observed on HSV-infected cells with EC50s of 6.1 μg/ml for HSV-1 and 3.8 μg/ml for HSV-2. These are the mean values from the test results of six batches of SPL7013. SPL7013 was also shown to be equally potent against HSV drug-resistant strains. SPL7013 completely inhibited viral adsorption to Vero cells at concentrations of higher than 3 μg/ml. Analyzed by a LightCycler assay after treatment of HSV-infected cells for 17 h, SPL7013 showed strong inhibition of HSV DNA synthesis with EC50s of approximately 6.2 and 2.0 μg/ml for HSV-1 and HSV-2, respectively. SPL7013 retained its anti-HSV activity even after treatment at acidic pHs 3.0 and 4.0 for 2 h. The presence of 10% human serum proteins did not affect the anti-HSV activity of SPL7013. SPL7013 was not toxic to Vero cells up to the highest concentration tested (10,000 μg/ml). Effects on cell proliferation were tested on two epithelial cell lines in both stationary and dividing phases. The 50% cytotoxic concentrations (CC50) in all cases were greater than 10,000 μg/ml. Our data indicate that SPL7013 is a promising candidate for development as a vaginal microbicide and a therapeutic agent.
Related Topics
Life Sciences
Immunology and Microbiology
Virology
Authors
Edwin Gong, Barry Matthews, Tom McCarthy, Jianhua Chu, George Holan, John Raff, Stephen Sacks,