A novel drug screening assay for papillomavirus specific antiviral activity

摘要: Discovery and development of human papillomavirus (HPV) specific antiviral agents have been hampered by the lack an in vitro assay permissive to HPV replication. An experimental system for monitoring HPV-11 DNA replication has optimized use as a drug screening tool. Cloned was introduced into SCC-4 cells electroporation viral monitored Southern blot. Kinetic studies demonstrated increased genome copy number with time. Viral replicated episomal, unit length remained episomal after multiple passages. These data suggested basis evaluating activity potential chemotherapeutic directly on HPV. This model used investigate activities current anti-HPV therapies such 5-fluorouracil (5-FU) alpha-interferon (alpha-IFN) sodium butyrate, 5-bromo-20-deoxyuridine (BrdU) antisense oligonucleotides. HPV- 11 is significantly inhibited BrdU butyrate; however 5-FU alpha-IFN did not give consistent dose response results. Finally, ISIS 2105, 20-mer phosphorothioate oligonucleotide, which targets E2 gene product, showed potent this IC50 approximately 70 nM.