Cargando…

Resolving a guanine-quadruplex structure in the SARS-CoV-2 genome through circular dichroism and multiscale molecular modeling

The genome of SARS-CoV-2 coronavirus is made up of a single-stranded RNA fragment that can assume a specific secondary structure, whose stability can influence the virus’s ability to reproduce. Recent studies have identified putative guanine quadruplex sequences in SARS-CoV-2 genome fragments that a...

Descripción completa

Detalles Bibliográficos
Autores principales: D'Anna, Luisa, Miclot, Tom, Bignon, Emmanuelle, Perricone, Ugo, Barone, Giampaolo, Monari, Antonio, Terenzi, Alessio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599604/
https://www.ncbi.nlm.nih.gov/pubmed/37886086
http://dx.doi.org/10.1039/d3sc04004f
_version_ 1785125801398632448
author D'Anna, Luisa
Miclot, Tom
Bignon, Emmanuelle
Perricone, Ugo
Barone, Giampaolo
Monari, Antonio
Terenzi, Alessio
author_facet D'Anna, Luisa
Miclot, Tom
Bignon, Emmanuelle
Perricone, Ugo
Barone, Giampaolo
Monari, Antonio
Terenzi, Alessio
author_sort D'Anna, Luisa
collection PubMed
description The genome of SARS-CoV-2 coronavirus is made up of a single-stranded RNA fragment that can assume a specific secondary structure, whose stability can influence the virus’s ability to reproduce. Recent studies have identified putative guanine quadruplex sequences in SARS-CoV-2 genome fragments that are involved in coding for both structural and non-structural proteins. In this contribution, we focus on a specific G-rich sequence referred to as RG-2, which codes for the non-structural protein 10 (Nsp10) and assumes a guanine-quadruplex (G4) arrangement. We provide the secondary structure of RG-2 G4 at atomistic resolution by molecular modeling and simulation, validated by the superposition of experimental and calculated electronic circular dichroism spectra. Through both experimental and simulation approaches, we have demonstrated that pyridostatin (PDS), a widely recognized G4 binder, can bind to and stabilize RG-2 G4 more strongly than RG-1, another G4 forming sequence that was previously proposed as a potential target for antiviral drug candidates. Overall, this study highlights RG-2 as a valuable target to inhibit the translation and replication of SARS-CoV-2, paving the way towards original therapeutic approaches against emerging RNA viruses.
format Online
Article
Text
id pubmed-10599604
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher The Royal Society of Chemistry
record_format MEDLINE/PubMed
spelling pubmed-105996042023-10-26 Resolving a guanine-quadruplex structure in the SARS-CoV-2 genome through circular dichroism and multiscale molecular modeling D'Anna, Luisa Miclot, Tom Bignon, Emmanuelle Perricone, Ugo Barone, Giampaolo Monari, Antonio Terenzi, Alessio Chem Sci Chemistry The genome of SARS-CoV-2 coronavirus is made up of a single-stranded RNA fragment that can assume a specific secondary structure, whose stability can influence the virus’s ability to reproduce. Recent studies have identified putative guanine quadruplex sequences in SARS-CoV-2 genome fragments that are involved in coding for both structural and non-structural proteins. In this contribution, we focus on a specific G-rich sequence referred to as RG-2, which codes for the non-structural protein 10 (Nsp10) and assumes a guanine-quadruplex (G4) arrangement. We provide the secondary structure of RG-2 G4 at atomistic resolution by molecular modeling and simulation, validated by the superposition of experimental and calculated electronic circular dichroism spectra. Through both experimental and simulation approaches, we have demonstrated that pyridostatin (PDS), a widely recognized G4 binder, can bind to and stabilize RG-2 G4 more strongly than RG-1, another G4 forming sequence that was previously proposed as a potential target for antiviral drug candidates. Overall, this study highlights RG-2 as a valuable target to inhibit the translation and replication of SARS-CoV-2, paving the way towards original therapeutic approaches against emerging RNA viruses. The Royal Society of Chemistry 2023-09-11 /pmc/articles/PMC10599604/ /pubmed/37886086 http://dx.doi.org/10.1039/d3sc04004f Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
D'Anna, Luisa
Miclot, Tom
Bignon, Emmanuelle
Perricone, Ugo
Barone, Giampaolo
Monari, Antonio
Terenzi, Alessio
Resolving a guanine-quadruplex structure in the SARS-CoV-2 genome through circular dichroism and multiscale molecular modeling
title Resolving a guanine-quadruplex structure in the SARS-CoV-2 genome through circular dichroism and multiscale molecular modeling
title_full Resolving a guanine-quadruplex structure in the SARS-CoV-2 genome through circular dichroism and multiscale molecular modeling
title_fullStr Resolving a guanine-quadruplex structure in the SARS-CoV-2 genome through circular dichroism and multiscale molecular modeling
title_full_unstemmed Resolving a guanine-quadruplex structure in the SARS-CoV-2 genome through circular dichroism and multiscale molecular modeling
title_short Resolving a guanine-quadruplex structure in the SARS-CoV-2 genome through circular dichroism and multiscale molecular modeling
title_sort resolving a guanine-quadruplex structure in the sars-cov-2 genome through circular dichroism and multiscale molecular modeling
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599604/
https://www.ncbi.nlm.nih.gov/pubmed/37886086
http://dx.doi.org/10.1039/d3sc04004f
work_keys_str_mv AT dannaluisa resolvingaguaninequadruplexstructureinthesarscov2genomethroughcirculardichroismandmultiscalemolecularmodeling
AT miclottom resolvingaguaninequadruplexstructureinthesarscov2genomethroughcirculardichroismandmultiscalemolecularmodeling
AT bignonemmanuelle resolvingaguaninequadruplexstructureinthesarscov2genomethroughcirculardichroismandmultiscalemolecularmodeling
AT perriconeugo resolvingaguaninequadruplexstructureinthesarscov2genomethroughcirculardichroismandmultiscalemolecularmodeling
AT baronegiampaolo resolvingaguaninequadruplexstructureinthesarscov2genomethroughcirculardichroismandmultiscalemolecularmodeling
AT monariantonio resolvingaguaninequadruplexstructureinthesarscov2genomethroughcirculardichroismandmultiscalemolecularmodeling
AT terenzialessio resolvingaguaninequadruplexstructureinthesarscov2genomethroughcirculardichroismandmultiscalemolecularmodeling