Human Papillomavirus G-Rich Regions as Potential Antiviral Drug Targets

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F21%3A00536202" target="_blank" >RIV/68081707:_____/21:00536202 - 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>

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

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

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nucleic Acid Therapeutics

ISSN

2159-3337

e-ISSN

2159-3345

Svazek periodika

31

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

68-81

Kód UT WoS článku

000586757700001

EID výsledku v databázi Scopus

2-s2.0-85100988111