A core extended naphtalene diimide G-quadruplex ligand potently inhibits herpes simplex virus 1 replication

Abstract G-quadruplexes (G4s) are nucleic acids secondary structures, epigenetic regulators in cells and viruses. In herpes simplex virus 1 (HSV-1)-infected cells, G4s are massively present during viral replication. We here aimed at investigating the possibility to target the HSV-1 G4s by a core ext...

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Autores principales:	Sara Callegaro, Rosalba Perrone, Matteo Scalabrin, Filippo Doria, Giorgio Palù, Sara N. Richter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3cce0b60960242b6831f570265d79d7b
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spelling	oai:doaj.org-article:3cce0b60960242b6831f570265d79d7b2021-12-02T11:52:40ZA core extended naphtalene diimide G-quadruplex ligand potently inhibits herpes simplex virus 1 replication10.1038/s41598-017-02667-32045-2322https://doaj.org/article/3cce0b60960242b6831f570265d79d7b2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02667-3https://doaj.org/toc/2045-2322Abstract G-quadruplexes (G4s) are nucleic acids secondary structures, epigenetic regulators in cells and viruses. In herpes simplex virus 1 (HSV-1)-infected cells, G4s are massively present during viral replication. We here aimed at investigating the possibility to target the HSV-1 G4s by a core extended naphtalene diimide (c-exNDI) G4 ligand. Biophysical and biomolecular analysis proved that c-exNDI stabilized the HSV-1 G4s in a concentration dependent manner. In MS competition assays, c-exNDI preferentially recognized HSV-1 G4s over cellular telomeric G4s, the most represented G4s within cells; other less abundant cellular G4s were also recognized. Treatment of HSV-1 infected cells with c-exNDI at low nanomolar concentrations induced significant virus inhibition with no cytotoxicity. The mechanism of action was ascribed to G4-mediated inhibition of viral DNA replication, with consequent impairment of viral genes transcription. Our data suggest that the observed potent antiviral activity and low cytotoxicity mainly depend on a combination of c-exNDI affinity for HSV-1 G4s and their massive presence during infection. HSV-1 G4s may thus represent new effective antiviral targets: the fact that no current antiherpetic drug exploits them and their presence at the viral genome, responsible for both active and latent HSV infections, makes them particularly attracting.Sara CallegaroRosalba PerroneMatteo ScalabrinFilippo DoriaGiorgio PalùSara N. RichterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sara Callegaro Rosalba Perrone Matteo Scalabrin Filippo Doria Giorgio Palù Sara N. Richter A core extended naphtalene diimide G-quadruplex ligand potently inhibits herpes simplex virus 1 replication
description	Abstract G-quadruplexes (G4s) are nucleic acids secondary structures, epigenetic regulators in cells and viruses. In herpes simplex virus 1 (HSV-1)-infected cells, G4s are massively present during viral replication. We here aimed at investigating the possibility to target the HSV-1 G4s by a core extended naphtalene diimide (c-exNDI) G4 ligand. Biophysical and biomolecular analysis proved that c-exNDI stabilized the HSV-1 G4s in a concentration dependent manner. In MS competition assays, c-exNDI preferentially recognized HSV-1 G4s over cellular telomeric G4s, the most represented G4s within cells; other less abundant cellular G4s were also recognized. Treatment of HSV-1 infected cells with c-exNDI at low nanomolar concentrations induced significant virus inhibition with no cytotoxicity. The mechanism of action was ascribed to G4-mediated inhibition of viral DNA replication, with consequent impairment of viral genes transcription. Our data suggest that the observed potent antiviral activity and low cytotoxicity mainly depend on a combination of c-exNDI affinity for HSV-1 G4s and their massive presence during infection. HSV-1 G4s may thus represent new effective antiviral targets: the fact that no current antiherpetic drug exploits them and their presence at the viral genome, responsible for both active and latent HSV infections, makes them particularly attracting.
format	article
author	Sara Callegaro Rosalba Perrone Matteo Scalabrin Filippo Doria Giorgio Palù Sara N. Richter
author_facet	Sara Callegaro Rosalba Perrone Matteo Scalabrin Filippo Doria Giorgio Palù Sara N. Richter
author_sort	Sara Callegaro
title	A core extended naphtalene diimide G-quadruplex ligand potently inhibits herpes simplex virus 1 replication
title_short	A core extended naphtalene diimide G-quadruplex ligand potently inhibits herpes simplex virus 1 replication
title_full	A core extended naphtalene diimide G-quadruplex ligand potently inhibits herpes simplex virus 1 replication
title_fullStr	A core extended naphtalene diimide G-quadruplex ligand potently inhibits herpes simplex virus 1 replication
title_full_unstemmed	A core extended naphtalene diimide G-quadruplex ligand potently inhibits herpes simplex virus 1 replication
title_sort	core extended naphtalene diimide g-quadruplex ligand potently inhibits herpes simplex virus 1 replication
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3cce0b60960242b6831f570265d79d7b
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A core extended naphtalene diimide G-quadruplex ligand potently inhibits herpes simplex virus 1 replication

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