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Journal of Virology, May 2001, p. 4117-4128, Vol. 75, No. 9
Integrated Program in Cellular, Molecular and
Biophysical Studies1 and Department of
Microbiology,2 College of Physicians and
Surgeons, Columbia University, New York, New York 10032
Received 4 October 2000/Accepted 30 January 2001
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 µg/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
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.9.4117-4128.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Herpes Simplex Virus Type 1 Entry Is Inhibited by
the Cobalt Chelate Complex CTC-96
mRNA
transcripts when CTC-96 is present at the onset of infection. Moreover,
virion-associated
TIF 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.
*
Corresponding author. Mailing address: Department of
Microbiology, College of Physicians and Surgeons, Columbia University, 701 W. 168th St., New York, NY 10032. Phone: (212) 305-8149. Fax: (212)
305-5106. E-mail: sjs6{at}columbia.edu.
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