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The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure the dimerization of angiotensin-converting enzyme 2 (ACE...

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Autores principales: Davies, Scott P., Mycroft-West, Courtney J., Pagani, Isabel, Hill, Harriet J., Chen, Yen-Hsi, Karlsson, Richard, Bagdonaite, Ieva, Guimond, Scott E., Stamataki, Zania, De Lima, Marcelo Andrade, Turnbull, Jeremy E., Yang, Zhang, Vicenzi, Elisa, Skidmore, Mark A., Khanim, Farhat L., Richardson, Alan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377159/
https://www.ncbi.nlm.nih.gov/pubmed/34421587
http://dx.doi.org/10.3389/fphar.2021.660490
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author Davies, Scott P.
Mycroft-West, Courtney J.
Pagani, Isabel
Hill, Harriet J.
Chen, Yen-Hsi
Karlsson, Richard
Bagdonaite, Ieva
Guimond, Scott E.
Stamataki, Zania
De Lima, Marcelo Andrade
Turnbull, Jeremy E.
Yang, Zhang
Vicenzi, Elisa
Skidmore, Mark A.
Khanim, Farhat L.
Richardson, Alan
author_facet Davies, Scott P.
Mycroft-West, Courtney J.
Pagani, Isabel
Hill, Harriet J.
Chen, Yen-Hsi
Karlsson, Richard
Bagdonaite, Ieva
Guimond, Scott E.
Stamataki, Zania
De Lima, Marcelo Andrade
Turnbull, Jeremy E.
Yang, Zhang
Vicenzi, Elisa
Skidmore, Mark A.
Khanim, Farhat L.
Richardson, Alan
author_sort Davies, Scott P.
collection PubMed
description The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure the dimerization of angiotensin-converting enzyme 2 (ACE2), the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate. Fenofibric acid also destabilized the receptor-binding domain (RBD) of the viral spike protein and inhibited RBD binding to ACE2 in enzyme-linked immunosorbent assay (ELISA) and whole cell-binding assays. Fenofibrate and fenofibric acid were tested by two independent laboratories measuring infection of cultured Vero cells using two different SARS-CoV-2 isolates. In both settings at drug concentrations, which are clinically achievable, fenofibrate and fenofibric acid reduced viral infection by up to 70%. Together with its extensive history of clinical use and its relatively good safety profile, this study identifies fenofibrate as a potential therapeutic agent requiring an urgent clinical evaluation to treat SARS-CoV-2 infection.
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spelling pubmed-83771592021-08-21 The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models Davies, Scott P. Mycroft-West, Courtney J. Pagani, Isabel Hill, Harriet J. Chen, Yen-Hsi Karlsson, Richard Bagdonaite, Ieva Guimond, Scott E. Stamataki, Zania De Lima, Marcelo Andrade Turnbull, Jeremy E. Yang, Zhang Vicenzi, Elisa Skidmore, Mark A. Khanim, Farhat L. Richardson, Alan Front Pharmacol Pharmacology The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure the dimerization of angiotensin-converting enzyme 2 (ACE2), the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate. Fenofibric acid also destabilized the receptor-binding domain (RBD) of the viral spike protein and inhibited RBD binding to ACE2 in enzyme-linked immunosorbent assay (ELISA) and whole cell-binding assays. Fenofibrate and fenofibric acid were tested by two independent laboratories measuring infection of cultured Vero cells using two different SARS-CoV-2 isolates. In both settings at drug concentrations, which are clinically achievable, fenofibrate and fenofibric acid reduced viral infection by up to 70%. Together with its extensive history of clinical use and its relatively good safety profile, this study identifies fenofibrate as a potential therapeutic agent requiring an urgent clinical evaluation to treat SARS-CoV-2 infection. Frontiers Media S.A. 2021-08-06 /pmc/articles/PMC8377159/ /pubmed/34421587 http://dx.doi.org/10.3389/fphar.2021.660490 Text en Copyright © 2021 Davies, Mycroft-West, Pagani, Hill, Chen, Karlsson, Bagdonaite, Guimond, Stamataki, De Lima, Turnbull, Yang, Vicenzi, Skidmore, Khanim and Richardson. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Davies, Scott P.
Mycroft-West, Courtney J.
Pagani, Isabel
Hill, Harriet J.
Chen, Yen-Hsi
Karlsson, Richard
Bagdonaite, Ieva
Guimond, Scott E.
Stamataki, Zania
De Lima, Marcelo Andrade
Turnbull, Jeremy E.
Yang, Zhang
Vicenzi, Elisa
Skidmore, Mark A.
Khanim, Farhat L.
Richardson, Alan
The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models
title The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models
title_full The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models
title_fullStr The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models
title_full_unstemmed The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models
title_short The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models
title_sort hyperlipidaemic drug fenofibrate significantly reduces infection by sars-cov-2 in cell culture models
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377159/
https://www.ncbi.nlm.nih.gov/pubmed/34421587
http://dx.doi.org/10.3389/fphar.2021.660490
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