Effect of novobiocin and other DNA gyrase inhibitors on virus replication and DNA synthesis in herpes simplex virus type 1-infected BHK cells.
The four known inhibitors of the bacterial DNA gyrase (nalidixic acid, oxolinic acid, novobiocin and coumermycin A) were investigated with respect to their effect on the growth of uninfected BHK cells and the yield of virus from herpes simplex virus type 1 (HSV-1)-infected BHK cells. High concentrations of nalidixic acid and oxolinic acid (about 10 mM) were needed for 50% inhibition of cellular and viral multiplication with less than fourfold preferential inhibition of virus over cell growth. Novobiocin and coumermycin were effective at lower molar concentrations and the amount needed for 50% inhibition was 10-fold higher for cell growth than for virus yield. At 5 x 10(-4) M, novobiocin inhibited DNA synthesis in uninfected cells to approx. 20% of non-treated controls, while virus DNA in infected cells was almost completely inhibited (approx. 1% of controls). Residual cellular DNA synthesis in infected cells was rather insensitive (approx. 90% of controls) to this concentration of novobiocin.
D049933:Aminocoumarins; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003374:Coumarins / Q000494:pharmacology; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis*; D004279:DNA, Viral / Q000096:biosynthesis*; D009268:Nalidixic Acid / Q000494:pharmacology; D009675:Novobiocin / Q000494:pharmacology*; D010093:Oxolinic Acid / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects*; D059005:Topoisomerase II Inhibitors; D014779:Virus Replication / Q000187:drug effects
D049933:Aminocoumarins; D003374:Coumarins; D004279:DNA, Viral; D011758:Pyrroles; D059005:Topoisomerase II Inhibitors; D009675:Novobiocin; D009268:Nalidixic Acid; D004247:DNA; D010093:Oxolinic Acid; C004628:coumermycin