Evaluation of dendrimer SPL7013, a lead microbicide candidate against herpes simplex viruses
| Autor: | Jianhua Chu, Barry Ross Matthews, George Holan, John Raff, Edwin Gong, Stephen L. Sacks, Mccarthy Thomas D |
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| Rok vydání: | 2005 |
| Předmět: |
Pharmacology
Dendrimers Cell growth Vaginal microbicide Herpesvirus 2 Human viruses Herpes Simplex Herpesvirus 1 Human Microbial Sensitivity Tests Biology Virus Replication Antiviral Agents Blood proteins Molecular biology In vitro Cell Line Microbiology Anti-Infective Agents Evaluation Studies as Topic Cell culture Virology Microbicide Vero cell Cytotoxic T cell Polylysine |
| Zdroj: | Antiviral Research. 68:139-146 |
| ISSN: | 0166-3542 |
| DOI: | 10.1016/j.antiviral.2005.08.004 |
| Popis: | 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 (EC(50)) determined by pre-treatment of cells were 2.0 microg/ml for HSV-1 and 0.5 microg/ml for HSV-2. Inhibitory effects were also observed on HSV-infected cells with EC(50)s of 6.1 microg/ml for HSV-1 and 3.8 microg/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 microg/ml. Analyzed by a LightCycler assay after treatment of HSV-infected cells for 17 h, SPL7013 showed strong inhibition of HSV DNA synthesis with EC(50)s of approximately 6.2 and 2.0 microg/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 microg/ml). Effects on cell proliferation were tested on two epithelial cell lines in both stationary and dividing phases. The 50% cytotoxic concentrations (CC(50)) in all cases were greater than 10,000 microg/ml. Our data indicate that SPL7013 is a promising candidate for development as a vaginal microbicide and a therapeutic agent. |
| Databáze: | OpenAIRE |
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