Human Papillomavirus G-Rich Regions as Potential Antiviral Drug Targets
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F20%3A00536202" target="_blank" >RIV/68081707:_____/20:00536202 - isvavai.cz</a>
Výsledek na webu
<a href="https://www.liebertpub.com/doi/full/10.1089/nat.2020.0869" target="_blank" >https://www.liebertpub.com/doi/full/10.1089/nat.2020.0869</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1089/nat.2020.0869" target="_blank" >10.1089/nat.2020.0869</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Human Papillomavirus G-Rich Regions as Potential Antiviral Drug Targets
Popis výsledku v původním jazyce
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, C-8 and pyridostatin, respectively. In addition, one of the selected compounds, the acridine derivative C-8, 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.
Název v anglickém jazyce
Human Papillomavirus G-Rich Regions as Potential Antiviral Drug Targets
Popis výsledku anglicky
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, C-8 and pyridostatin, respectively. In addition, one of the selected compounds, the acridine derivative C-8, 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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10608 - Biochemistry and molecular biology
Návaznosti výsledku
Projekt
<a href="/cs/project/EF15_003%2F0000477" target="_blank" >EF15_003/0000477: Strukturní gymnastika nukleových kyselin: od molekulárních principů přes biologické funkce k terapeutickým cílům.</a><br>
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Nucleic Acid Therapeutics
ISSN
2159-3337
e-ISSN
—
Svazek periodika
2020
Číslo periodika v rámci svazku
2020
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
14
Strana od-do
—
Kód UT WoS článku
000586757700001
EID výsledku v databázi Scopus
2-s2.0-85100988111