Herein, we report, for the first time, the screening of several ligands in terms of their ability to bind and stabilize G-quadruplexes (G4) found in seven human Papillomavirus (HPV) genomes. Using a variety of biophysical assays, HPV G-quadruplexes were shown to possess a high degree of structural polymorphism upon ligand binding, which may have an impact on transcription, replication, and viral protein production. A sequence found in high-risk HPV16 genotype folds into multiple non-canonical DNA structures; it was converted into a major G4 conformation upon interaction with a well-characterized highly selective G4 ligand, PhenDC3, which may have an impact on the viral infection. Likewise, HPV57 and 58, which fold into multiple G4 structures, were found to form single stable complexes in the presence of two other G4 ligands, C8 and pyridostatin, respectively. In addition, one of the selected compounds, the acridine derivative C8, demonstrated a significant antiviral effect in HPV18-infected organotypic raft cultures. Altogether, these results indicate that targeting HPV G4s may be an alternative route for the development of novel antiviral therapies.
- MeSH
- aminochinoliny farmakologie MeSH
- cílená molekulární terapie MeSH
- DNA vazebné proteiny genetika MeSH
- G-kvadruplexy účinky léků MeSH
- genom virový účinky léků genetika MeSH
- genotyp MeSH
- komplement C8 genetika farmakologie MeSH
- konformace nukleové kyseliny účinky léků MeSH
- kyseliny pikolinové farmakologie MeSH
- lidé MeSH
- lidský papilomavirus 16 účinky léků genetika patogenita ultrastruktura MeSH
- lidský papilomavirus 18 účinky léků genetika ultrastruktura MeSH
- ligandy MeSH
- virové nemoci farmakoterapie genetika patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
