Inhibition of Simian virus 40 large T antigen helicase activity by fluoroquinolones.
BACKGROUND
Fluoroquinolones represent a potent group of antibiotics that inhibit bacterial DNA replication by targeting the essential bacterial enzymes gyrase and topoisomerase IV. Inhibition of gyrase activity by quinolones involves the interaction of these drugs with the helicase component of bacterial gyrase. DNA tumour viruses also encode helicases that are essential for their DNA replication in the host.


METHODS
In this study we have evaluated the effect of fluoroquinolones on viral DNA replication using the DNA tumour virus Simian virus 40 (SV40) as our model. Four different fluoroquinolones, namely, levofloxacin, trovafloxacin, ciprofloxacin and ofloxacin, were tested for their ability to inhibit viral DNA replication.


RESULTS
We show here that all four quinolones tested were effective in the inhibition of SV40 plaque formation and DNA replication in CV1-P cells. In addition, we found that each of these quinolones was inhibitory to the helicase activity of SV40 large tumour antigen.


CONCLUSIONS
Fluoroquinolones and their derivates may therefore be useful in the treatment and/or prevention of infection by SV40-homologous human DNA viruses that encode helicase activity for their survival.
Ali
Syed Hamid
SH
Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi, Pakistan. syed.ali@aku.edu
Chandraker
Anil
A
DeCaprio
James A
JA
D000952:Antigens, Polyomavirus Transforming / Q000187:drug effects* / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002939:Ciprofloxacin / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004265:DNA Helicases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000096:biosynthesis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D064704:Levofloxacin; D009287:Naphthyridines / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D015203:Reproducibility of Results; D013539:Simian virus 40 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D013997:Time Factors; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
D000952:Antigens, Polyomavirus Transforming; D000998:Antiviral Agents; D004279:DNA, Viral; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D009287:Naphthyridines; D002939:Ciprofloxacin; D064704:Levofloxacin; C080163:trovafloxacin; D015242:Ofloxacin; D004265:DNA Helicases