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Effects of the Natural Flavonoid Quercetin on Arenavirus Junín Infection

There is no specific chemotherapy approved for the treatment of pathogenic arenaviruses that cause severe hemorrhagic fever (HF) in the population of endemic regions in America and Africa. The present study reports the effects of the natural flavonoid quercetin (QUER) on the infection of A549 and Ve...

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Autores principales: Alvarez De Lauro, Aaron Ezequiel, Pelaez, Miguel Angel, Marquez, Agostina Belén, Wagner, Mariel Selene, Scolaro, Luis Alberto, García, Cybele Carina, Damonte, Elsa Beatriz, Sepúlveda, Claudia Soledad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10459926/
https://www.ncbi.nlm.nih.gov/pubmed/37632083
http://dx.doi.org/10.3390/v15081741
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author Alvarez De Lauro, Aaron Ezequiel
Pelaez, Miguel Angel
Marquez, Agostina Belén
Wagner, Mariel Selene
Scolaro, Luis Alberto
García, Cybele Carina
Damonte, Elsa Beatriz
Sepúlveda, Claudia Soledad
author_facet Alvarez De Lauro, Aaron Ezequiel
Pelaez, Miguel Angel
Marquez, Agostina Belén
Wagner, Mariel Selene
Scolaro, Luis Alberto
García, Cybele Carina
Damonte, Elsa Beatriz
Sepúlveda, Claudia Soledad
author_sort Alvarez De Lauro, Aaron Ezequiel
collection PubMed
description There is no specific chemotherapy approved for the treatment of pathogenic arenaviruses that cause severe hemorrhagic fever (HF) in the population of endemic regions in America and Africa. The present study reports the effects of the natural flavonoid quercetin (QUER) on the infection of A549 and Vero cells with Junín virus (JUNV), agent of the Argentine HF. By infectivity assays, a very effective dose-dependent reduction of JUNV multiplication was shown by cell pretreatment at 2–6 h prior to the infection at non-cytotoxic concentrations, with 50% effective concentration values in the range of 6.1–7.5 µg/mL. QUER was also active by post-infection treatment but with minor efficacy. Mechanistic studies indicated that QUER mainly affected the early steps of virus adsorption and internalization in the multiplication cycle of JUNV. Treatment with QUER blocked the phosphorylation of Akt without changes in the total protein expression, detected by Western blot, and the consequent perturbation of the PI3K/Akt pathway was also associated with the fluorescence redistribution from membrane to cytoplasm of TfR1, the cell receptor recognized by JUNV. Then, it appears that the cellular antiviral state, induced by QUER treatment, leads to the prevention of JUNV entry into the cell.
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spelling pubmed-104599262023-08-27 Effects of the Natural Flavonoid Quercetin on Arenavirus Junín Infection Alvarez De Lauro, Aaron Ezequiel Pelaez, Miguel Angel Marquez, Agostina Belén Wagner, Mariel Selene Scolaro, Luis Alberto García, Cybele Carina Damonte, Elsa Beatriz Sepúlveda, Claudia Soledad Viruses Article There is no specific chemotherapy approved for the treatment of pathogenic arenaviruses that cause severe hemorrhagic fever (HF) in the population of endemic regions in America and Africa. The present study reports the effects of the natural flavonoid quercetin (QUER) on the infection of A549 and Vero cells with Junín virus (JUNV), agent of the Argentine HF. By infectivity assays, a very effective dose-dependent reduction of JUNV multiplication was shown by cell pretreatment at 2–6 h prior to the infection at non-cytotoxic concentrations, with 50% effective concentration values in the range of 6.1–7.5 µg/mL. QUER was also active by post-infection treatment but with minor efficacy. Mechanistic studies indicated that QUER mainly affected the early steps of virus adsorption and internalization in the multiplication cycle of JUNV. Treatment with QUER blocked the phosphorylation of Akt without changes in the total protein expression, detected by Western blot, and the consequent perturbation of the PI3K/Akt pathway was also associated with the fluorescence redistribution from membrane to cytoplasm of TfR1, the cell receptor recognized by JUNV. Then, it appears that the cellular antiviral state, induced by QUER treatment, leads to the prevention of JUNV entry into the cell. MDPI 2023-08-15 /pmc/articles/PMC10459926/ /pubmed/37632083 http://dx.doi.org/10.3390/v15081741 Text en © 2023 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
Alvarez De Lauro, Aaron Ezequiel
Pelaez, Miguel Angel
Marquez, Agostina Belén
Wagner, Mariel Selene
Scolaro, Luis Alberto
García, Cybele Carina
Damonte, Elsa Beatriz
Sepúlveda, Claudia Soledad
Effects of the Natural Flavonoid Quercetin on Arenavirus Junín Infection
title Effects of the Natural Flavonoid Quercetin on Arenavirus Junín Infection
title_full Effects of the Natural Flavonoid Quercetin on Arenavirus Junín Infection
title_fullStr Effects of the Natural Flavonoid Quercetin on Arenavirus Junín Infection
title_full_unstemmed Effects of the Natural Flavonoid Quercetin on Arenavirus Junín Infection
title_short Effects of the Natural Flavonoid Quercetin on Arenavirus Junín Infection
title_sort effects of the natural flavonoid quercetin on arenavirus junín infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10459926/
https://www.ncbi.nlm.nih.gov/pubmed/37632083
http://dx.doi.org/10.3390/v15081741
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