Article In: orcid, cienciavitae

Human Papillomavirus G-Rich Regions as Potential Antiviral Drug Targets

Nucleic Acid Therapeutics

Carvalho, Josué; Lopes-Nunes, Jéssica; et al — 2021 — Mary Ann Liebert, Inc.

Key information

Authors:

Carvalho, Josué; Lopes-Nunes, Jéssica; Campello, Maria Paula Cabral (Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros); Paulo, António (António Manuel Rocha Paulo); Milici, Janice; Meyers, Craig; Mergny, Jean-Louis; et al

Published in

02/11/2021

Abstract

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.

Publication details

Authors in the community:

Publication version

VoR - Version of Record

Publisher

Mary Ann Liebert, Inc.

Link to the publisher's version

https://www.liebertpub.com/journal/nat

Title of the publication container

Nucleic Acid Therapeutics

First page or article number

68

Last page

81

Volume

31

Issue

1

ISSN

2159-3337

DOI

10.1089/nat.2020.0869

WoS (Web of Science)

WOS:000586757700001

Fields of Science and Technology (FOS)

chemical-sciences - Chemical sciences

Keywords

  • human papillomavirus
  • G-quadruplex
  • antiviral
  • ligands
  • organotypic rafts

Publication language (ISO code)

eng - English

Alternative identifier (URI)

http://dx.doi.org/10.1089/nat.2020.0869

Rights type:

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