Herpes simplex virus type 1 entry is inhibited by the cobalt chelate complex CTC-96.

Abstract

The CTC series of cobalt chelates display in vitro and in vivo activity against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). The experiments described here identify the stage in the virus life cycle where CTC-96 acts and demonstrate that the drug inhibits infection of susceptible cells. CTC-96 at 50 microg/ml has no effect on adsorption of virions to Vero cell monolayers. Penetration assays reveal that CTC-96 inhibits entry of the virus independent of gC and cellular entry receptors. This observation was supported by the failure to detect the accumulation of virus-specified proteins and alpha mRNA transcripts when CTC-96 is present at the onset of infection. Moreover, virion-associated alphaTIF does not accumulate in the nucleus of cells infected in the presence of CTC-96. CTC-96 targets the initial fusion event between the virus and the cell and also inhibits cell-to-cell spread and syncytium formation. Furthermore, CTC-96 inhibits plaque formation by varicella-zoster virus and vesicular stomatitis virus as efficiently as by HSV-1. Collectively, these experiments suggest that CTC-96 is a broad-spectrum inhibitor of infection by enveloped viruses and that it inhibits HSV-1 infection at the point of membrane fusion independent of the type of virus and cellular receptors present.

• Authors: J A Schwartz, E K Lium, S J Silverstein
• Journal: Journal of virology (J Virol) Vol. 75 Issue 9 Pg. 4117-28 (May 2001) ISSN: 0022-538X [Print] United States
• PMID: 11287561 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antiviral Agents
• Herpes Simplex Virus Protein Vmw65
• Organometallic Compounds
• RNA, Messenger
• Receptors, Virus
• Viral Envelope Proteins
• Viral Proteins
• glycoprotein gC, herpes simplex virus type 1
• CTC 96
• Cobalt

Topics

• Animals
• Antiviral Agents (chemistry, pharmacology)
• CHO Cells
• Cell Nucleus (metabolism)
• Chlorocebus aethiops
• Cobalt (pharmacology)
• Cricetinae
• Herpes Simplex Virus Protein Vmw65 (metabolism)
• Herpesvirus 1, Human (drug effects, metabolism, physiology)
• Herpesvirus 3, Human (drug effects)
• Humans
• Molecular Structure
• Organometallic Compounds (chemistry, pharmacology)
• RNA, Messenger
• Receptors, Virus (metabolism)
• Vero Cells
• Viral Envelope Proteins (metabolism)
• Viral Proteins (metabolism)
• Virus Replication (drug effects)