Dynamics of the antiviral activity of N-methanocarbathymidine against herpes simplex virus type 1 in cell culture.
N-Methanocarbathymidine [(N)-MCT], a thymidine analogue, exhibits potent activity in cell culture against herpes simplex virus1 (HSV-1). (N)-MCT showed higher antiviral activity than ganciclovir (GCV). Continuous treatment of Vero cells with (N)-MCT immediately or 10 h post-infection (p.i.) fully prevented the development of viral infection. However, when infected cells were treated with (N)-MCT at 12 h p.i., there was only a partial inhibition (ca. 50%). Additionally, continuous treatment of infected cells with (N)-MCT for about 48 h was sufficient to achieve full prevention of viral infection without further treatment. These findings suggest the complete loss of herpes simplex thymidine kinase (HSV-tk) activity occurs after 48 h of treatment with (N)-MCT. This study helps to understand the mechanism and dynamics of antiHSV activity of (N)-MCT, which is necessary for its future development as an antiviral drug.
Huleihel
Mahmoud
M
The Institute for Applied Biosciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel. mahmoudh@bgumail.bgu.ac.il
Talishanisky
Marina
M
Ford
Harry
H
Marquez
Victor E
VE
Kelley
James A
JA
Johns
David G
DG
Agbaria
Riad
R
D000818:Animals; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000254:growth & development; D013936:Thymidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
C469995:(north)-methanocarbathymidine; D013936:Thymidine