On the complex nature of the antiviral activity of coumermycin A1: its interference with the replication of herpes simplex virus type 1.
The mechanism of inhibition of the replication of herpes simplex virus type 1 (HSV-1) by coumermycin A1 (CA1), an inhibitor of bacterial DNA gyrase, has been investigated. Concentrations of antibiotic slightly higher than those needed for 50% inhibition of viral growth were able to inhibit viral DNA synthesis in infected cells. This effect was accompanied by a depressed synthesis of viral polypeptides. Protein synthesis was also inhibited in uninfected cells, especially after long exposure to the drug, but not in a cell-free system. In vitro assays of highly purified HSV-1 DNA polymerase in the presence of the drug, provided evidence that the enzyme was a target of CA1. The viral polymerase was in fact inhibited by the antibiotic to an extent comparable to that of viral DNA synthesis in intact cells. In contrast, DNA polymerase alpha, the enzyme involved in chromosomal DNA replication, was relatively insensitive to CA1. The drug was also shown to bind to protein and to viral and cellular DNA.
D049933:Aminocoumarins; D002460:Cell Line; D003374:Coumarins / Q000378:metabolism / Q000494:pharmacology; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000096:biosynthesis; D004259:DNA-Directed DNA Polymerase; D005090:Exodeoxyribonucleases / Q000037:antagonists & inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D010452:Peptide Biosynthesis; D018139:Simplexvirus / Q000187:drug effects*; D059005:Topoisomerase II Inhibitors; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
D049933:Aminocoumarins; D003374:Coumarins; D004279:DNA, Viral; D019384:Nucleic Acid Synthesis Inhibitors; D059005:Topoisomerase II Inhibitors; D014764:Viral Proteins; D004257:DNA Polymerase II; D004259:DNA-Directed DNA Polymerase; D005090:Exodeoxyribonucleases; C043417:DNA polymerase, Simplexvirus; C004628:coumermycin