Antiviral activity of CTC-8 against herpes simplex virus (HSV-1) in cell culture: evidence for a selective antiviral effect via a cellular mechanism.
A synthetic programme produced a series of compounds related to natural prostaglandins, which are known to affect the growth of a number of viruses. Several of the compounds showed potent biological activity including antiviral effects. The compound CTC-8 [(S)-4-tert-butyldimethylsilyloxy-2-cyclopenten-1-one] contains the cyclopentenone ring of prostaglandin A1, but the extended side chains common to the prostaglandin family are truncated. The present study demonstrates that CTC-8 inhibits HSV-1 replication in cell culture at sub-toxic concentrations. The antiviral effect was evidenced by reduction in infectious virus yield, although the compound was not effective in the standard plaque-reduction assay. Time-of-addition studies and other experiments provide a possible explanation for these results by suggesting that the antiviral activity is confined to a single cycle. Under the standard conditions of high-multiplicity infection in BHK cells it was notable that CTC-8 is most effective when added for a short period 6-8 h post-infection. Furthermore, multiple passage of HSV-1 in the presence of CTC-8 did not result in the selection of resistant mutants. The results of these and other experiments are consistent with the hypothesis that the mechanism by which CTC-8 inhibits virus replication involves a cellular target. These results encourage further research into the therapeutic potential of this series of compounds.
Centre for Veterinary Science, University of Cambridge, Cambridge, UK.
Tim
T
Fitzmaurice
David R
DR
Harper
Hugh J
HJ
Field
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003517:Cyclopentanes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D024882:Drug Resistance, Viral; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D015394:Molecular Structure; D013997:Time Factors; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
C486212:(S)-4-tert-butyldimethylsilyloxy-2-cyclopenten-1-one; D000998:Antiviral Agents; D003517:Cyclopentanes