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Fullerene Derivatives Prevent Packaging of Viral Genomic RNA into HIV-1 Particles by Binding Nucleocapsid Protein

Fullerene derivatives with hydrophilic substituents have been shown to exhibit a range of biological activities, including antiviral ones. For a long time, the anti-HIV activity of fullerene derivatives was believed to be due to their binding into the hydrophobic pocket of HIV-1 protease, thereby bl...

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Autores principales: Křížová, Ivana, Dostálková, Alžběta, Castro, Edison, Prchal, Jan, Hadravová, Romana, Kaufman, Filip, Hrabal, Richard, Ruml, Tomáš, Llano, Manuel, Echegoyen, Luis, Rumlová, Michaela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705927/
https://www.ncbi.nlm.nih.gov/pubmed/34960720
http://dx.doi.org/10.3390/v13122451
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author Křížová, Ivana
Dostálková, Alžběta
Castro, Edison
Prchal, Jan
Hadravová, Romana
Kaufman, Filip
Hrabal, Richard
Ruml, Tomáš
Llano, Manuel
Echegoyen, Luis
Rumlová, Michaela
author_facet Křížová, Ivana
Dostálková, Alžběta
Castro, Edison
Prchal, Jan
Hadravová, Romana
Kaufman, Filip
Hrabal, Richard
Ruml, Tomáš
Llano, Manuel
Echegoyen, Luis
Rumlová, Michaela
author_sort Křížová, Ivana
collection PubMed
description Fullerene derivatives with hydrophilic substituents have been shown to exhibit a range of biological activities, including antiviral ones. For a long time, the anti-HIV activity of fullerene derivatives was believed to be due to their binding into the hydrophobic pocket of HIV-1 protease, thereby blocking its activity. Recent work, however, brought new evidence of a novel, protease-independent mechanism of fullerene derivatives’ action. We studied in more detail the mechanism of the anti-HIV-1 activity of N,N-dimethyl[70]fulleropyrrolidinium iodide fullerene derivatives. By using a combination of in vitro and cell-based approaches, we showed that these C(70) derivatives inhibited neither HIV-1 protease nor HIV-1 maturation. Instead, our data indicate effects of fullerene C(70) derivatives on viral genomic RNA packaging and HIV-1 cDNA synthesis during reverse transcription—without impairing reverse transcriptase activity though. Molecularly, this could be explained by a strong binding affinity of these fullerene derivatives to HIV-1 nucleocapsid domain, preventing its proper interaction with viral genomic RNA, thereby blocking reverse transcription and HIV-1 infectivity. Moreover, the fullerene derivatives’ oxidative activity and fluorescence quenching, which could be one of the reasons for the inconsistency among reported anti-HIV-1 mechanisms, are discussed herein.
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spelling pubmed-87059272021-12-25 Fullerene Derivatives Prevent Packaging of Viral Genomic RNA into HIV-1 Particles by Binding Nucleocapsid Protein Křížová, Ivana Dostálková, Alžběta Castro, Edison Prchal, Jan Hadravová, Romana Kaufman, Filip Hrabal, Richard Ruml, Tomáš Llano, Manuel Echegoyen, Luis Rumlová, Michaela Viruses Article Fullerene derivatives with hydrophilic substituents have been shown to exhibit a range of biological activities, including antiviral ones. For a long time, the anti-HIV activity of fullerene derivatives was believed to be due to their binding into the hydrophobic pocket of HIV-1 protease, thereby blocking its activity. Recent work, however, brought new evidence of a novel, protease-independent mechanism of fullerene derivatives’ action. We studied in more detail the mechanism of the anti-HIV-1 activity of N,N-dimethyl[70]fulleropyrrolidinium iodide fullerene derivatives. By using a combination of in vitro and cell-based approaches, we showed that these C(70) derivatives inhibited neither HIV-1 protease nor HIV-1 maturation. Instead, our data indicate effects of fullerene C(70) derivatives on viral genomic RNA packaging and HIV-1 cDNA synthesis during reverse transcription—without impairing reverse transcriptase activity though. Molecularly, this could be explained by a strong binding affinity of these fullerene derivatives to HIV-1 nucleocapsid domain, preventing its proper interaction with viral genomic RNA, thereby blocking reverse transcription and HIV-1 infectivity. Moreover, the fullerene derivatives’ oxidative activity and fluorescence quenching, which could be one of the reasons for the inconsistency among reported anti-HIV-1 mechanisms, are discussed herein. MDPI 2021-12-06 /pmc/articles/PMC8705927/ /pubmed/34960720 http://dx.doi.org/10.3390/v13122451 Text en © 2021 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
Křížová, Ivana
Dostálková, Alžběta
Castro, Edison
Prchal, Jan
Hadravová, Romana
Kaufman, Filip
Hrabal, Richard
Ruml, Tomáš
Llano, Manuel
Echegoyen, Luis
Rumlová, Michaela
Fullerene Derivatives Prevent Packaging of Viral Genomic RNA into HIV-1 Particles by Binding Nucleocapsid Protein
title Fullerene Derivatives Prevent Packaging of Viral Genomic RNA into HIV-1 Particles by Binding Nucleocapsid Protein
title_full Fullerene Derivatives Prevent Packaging of Viral Genomic RNA into HIV-1 Particles by Binding Nucleocapsid Protein
title_fullStr Fullerene Derivatives Prevent Packaging of Viral Genomic RNA into HIV-1 Particles by Binding Nucleocapsid Protein
title_full_unstemmed Fullerene Derivatives Prevent Packaging of Viral Genomic RNA into HIV-1 Particles by Binding Nucleocapsid Protein
title_short Fullerene Derivatives Prevent Packaging of Viral Genomic RNA into HIV-1 Particles by Binding Nucleocapsid Protein
title_sort fullerene derivatives prevent packaging of viral genomic rna into hiv-1 particles by binding nucleocapsid protein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705927/
https://www.ncbi.nlm.nih.gov/pubmed/34960720
http://dx.doi.org/10.3390/v13122451
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