Herpes simplex virus type 1 entry is inhibited by the cobalt chelate complex CTC-96.
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.
Schwartz
J A
JA
Integrated Program in Cellular, Molecular and Biophysical Studies, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Lium
E K
EK
Silverstein
S J
SJ
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D003035:Cobalt / Q000494:pharmacology*; D006224:Cricetinae; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014645:Herpesvirus 3, Human / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger; D011991:Receptors, Virus / Q000378:metabolism; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D017405:Herpes Simplex Virus Protein Vmw65; D009942:Organometallic Compounds; D012333:RNA, Messenger; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C038535:glycoprotein gC, herpes simplex virus type 1; C089809:CTC 96; D003035:Cobalt