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Binding Properties of RNA Quadruplex of SARS-CoV-2 to Berberine Compared to Telomeric DNA Quadruplex

Previous studies suggest that berberine, an isoquinoline alkaloid, has antiviral potential and is a possible therapeutic candidate against SARS-CoV-2. The molecular underpinnings of its action are still unknown. Potential targets include quadruplexes (G4Q) in the viral genome as they play a key role...

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Autores principales: Oliva, Rosario, Mukherjee, Sanjib, Manisegaran, Magiliny, Campanile, Marco, Del Vecchio, Pompea, Petraccone, Luigi, Winter, Roland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145931/
https://www.ncbi.nlm.nih.gov/pubmed/35628500
http://dx.doi.org/10.3390/ijms23105690
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author Oliva, Rosario
Mukherjee, Sanjib
Manisegaran, Magiliny
Campanile, Marco
Del Vecchio, Pompea
Petraccone, Luigi
Winter, Roland
author_facet Oliva, Rosario
Mukherjee, Sanjib
Manisegaran, Magiliny
Campanile, Marco
Del Vecchio, Pompea
Petraccone, Luigi
Winter, Roland
author_sort Oliva, Rosario
collection PubMed
description Previous studies suggest that berberine, an isoquinoline alkaloid, has antiviral potential and is a possible therapeutic candidate against SARS-CoV-2. The molecular underpinnings of its action are still unknown. Potential targets include quadruplexes (G4Q) in the viral genome as they play a key role in modulating the biological activity of viruses. While several DNA-G4Q structures and their binding properties have been elucidated, RNA-G4Qs such as RG-1 of the N-gene of SARS-CoV-2 are less explored. Using biophysical techniques, the berberine binding thermodynamics and the associated conformational and hydration changes of RG-1 could be characterized and compared with human telomeric DNA-G4Q 22AG. Berberine can interact with both quadruplexes. Substantial changes were observed in the interaction of berberine with 22AG and RG-1, which adopt different topologies that can also change upon ligand binding. The strength of interaction and the thermodynamic signatures were found to dependent not only on the initial conformation of the quadruplex, but also on the type of salt present in solution. Since berberine has shown promise as a G-quadruplex stabilizer that can modulate viral gene expression, this study may also contribute to the development of optimized ligands that can discriminate between binding to DNA and RNA G-quadruplexes.
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spelling pubmed-91459312022-05-29 Binding Properties of RNA Quadruplex of SARS-CoV-2 to Berberine Compared to Telomeric DNA Quadruplex Oliva, Rosario Mukherjee, Sanjib Manisegaran, Magiliny Campanile, Marco Del Vecchio, Pompea Petraccone, Luigi Winter, Roland Int J Mol Sci Article Previous studies suggest that berberine, an isoquinoline alkaloid, has antiviral potential and is a possible therapeutic candidate against SARS-CoV-2. The molecular underpinnings of its action are still unknown. Potential targets include quadruplexes (G4Q) in the viral genome as they play a key role in modulating the biological activity of viruses. While several DNA-G4Q structures and their binding properties have been elucidated, RNA-G4Qs such as RG-1 of the N-gene of SARS-CoV-2 are less explored. Using biophysical techniques, the berberine binding thermodynamics and the associated conformational and hydration changes of RG-1 could be characterized and compared with human telomeric DNA-G4Q 22AG. Berberine can interact with both quadruplexes. Substantial changes were observed in the interaction of berberine with 22AG and RG-1, which adopt different topologies that can also change upon ligand binding. The strength of interaction and the thermodynamic signatures were found to dependent not only on the initial conformation of the quadruplex, but also on the type of salt present in solution. Since berberine has shown promise as a G-quadruplex stabilizer that can modulate viral gene expression, this study may also contribute to the development of optimized ligands that can discriminate between binding to DNA and RNA G-quadruplexes. MDPI 2022-05-19 /pmc/articles/PMC9145931/ /pubmed/35628500 http://dx.doi.org/10.3390/ijms23105690 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Oliva, Rosario
Mukherjee, Sanjib
Manisegaran, Magiliny
Campanile, Marco
Del Vecchio, Pompea
Petraccone, Luigi
Winter, Roland
Binding Properties of RNA Quadruplex of SARS-CoV-2 to Berberine Compared to Telomeric DNA Quadruplex
title Binding Properties of RNA Quadruplex of SARS-CoV-2 to Berberine Compared to Telomeric DNA Quadruplex
title_full Binding Properties of RNA Quadruplex of SARS-CoV-2 to Berberine Compared to Telomeric DNA Quadruplex
title_fullStr Binding Properties of RNA Quadruplex of SARS-CoV-2 to Berberine Compared to Telomeric DNA Quadruplex
title_full_unstemmed Binding Properties of RNA Quadruplex of SARS-CoV-2 to Berberine Compared to Telomeric DNA Quadruplex
title_short Binding Properties of RNA Quadruplex of SARS-CoV-2 to Berberine Compared to Telomeric DNA Quadruplex
title_sort binding properties of rna quadruplex of sars-cov-2 to berberine compared to telomeric dna quadruplex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145931/
https://www.ncbi.nlm.nih.gov/pubmed/35628500
http://dx.doi.org/10.3390/ijms23105690
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