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Herpes simplex virus type 1 entry is inhibited by the cobalt chelate complex CTC-96
J A Schwartz1, E K Lium, S J Silverstein
1Integrated Program in Cellular, Molecular and Biophysical Studies, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Journal of Virology
|April 5, 2001
Summary
The cobalt chelate CTC-96 effectively inhibits herpes simplex virus (HSV) infection by blocking viral entry into cells. This broad-spectrum antiviral agent also shows promise against other enveloped viruses, targeting the crucial membrane fusion step.
Area of Science:
- Virology
- Antiviral Drug Discovery
- Molecular Biology
Background:
- Herpes simplex virus (HSV) infections remain a significant public health concern, necessitating the development of novel antiviral therapies.
- Cobalt chelates, including the CTC series, have demonstrated in vitro and in vivo antiviral activity against HSV types 1 and 2 (HSV-1 and HSV-2).
Purpose of the Study:
- To elucidate the mechanism of action of CTC-96 against HSV-1 infection.
- To determine the specific stage in the viral life cycle targeted by CTC-96.
- To assess the spectrum of antiviral activity of CTC-96 against other enveloped viruses.
Main Methods:
- Infection assays using Vero cell monolayers to evaluate viral adsorption and entry.
- Analysis of viral protein and mRNA transcript accumulation in the presence of CTC-96.
- Assessment of CTC-96's effect on cell-to-cell spread and syncytium formation.
- Plaque formation assays with HSV-1, varicella-zoster virus, and vesicular stomatitis virus.
Main Results:
- CTC-96 does not affect viral adsorption to cells.
- CTC-96 inhibits viral entry independently of glycoprotein C (gC) and cellular receptors.
- The drug prevents the accumulation of viral proteins and alpha mRNA transcripts.
- CTC-96 inhibits the nuclear accumulation of virion-associated alphaTIF.
- CTC-96 targets the initial virus-cell membrane fusion event, inhibiting cell-to-cell spread and syncytium formation.
- CTC-96 demonstrates potent inhibition of plaque formation for HSV-1, varicella-zoster virus, and vesicular stomatitis virus.
Conclusions:
- CTC-96 acts at the critical membrane fusion stage of HSV-1 infection, independent of viral and cellular receptors.
- CTC-96 exhibits broad-spectrum antiviral activity against enveloped viruses.
- CTC-96 represents a promising therapeutic agent for treating infections caused by a range of enveloped viruses.