Artigo De: orcid, cienciavitae
Human Papillomavirus G-Rich Regions as Potential Antiviral Drug Targets
Nucleic Acid Therapeutics
2021 — Mary Ann Liebert, Inc.
—Informações chave
Autores:
Publicado em
11/02/2021
Resumo
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.
Detalhes da publicação
Autores da comunidade :
António Manuel Rocha Paulo
ist126677
Versão da publicação
VoR - Versão publicada
Editora
Mary Ann Liebert, Inc.
Ligação para a versão da editora
https://www.liebertpub.com/journal/nat
Título do contentor da publicação
Nucleic Acid Therapeutics
Primeira página ou número de artigo
68
Última página
81
Volume
31
Fascículo
1
ISSN
2159-3337
WoS (Web of Science)
Domínio Científico (FOS)
chemical-sciences - Química
Palavras-chave
- human papillomavirus
- G-quadruplex
- antiviral
- ligands
- organotypic rafts
Idioma da publicação (código ISO)
eng - Inglês
Identificador alternativo (URI)
http://dx.doi.org/10.1089/nat.2020.0869
Acesso à publicação:
Acesso apenas a metadados