SP Davies
The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models.
Davies, SP; Mycroft-West, CJ; Pagani, I; Hill, HJ; Chen, Y-H; Karlsson, R; Bagdonaite, I; Guimond, S; Stamataki, Z; Andrade De Lima, M; Turnbull, JE; Yang, Z; Vicenzi, E; Skidmore, M; Khanim, FL; Richardson, A
Authors
CJ Mycroft-West
I Pagani
HJ Hill
Y-H Chen
R Karlsson
I Bagdonaite
Scott Guimond s.e.guimond@keele.ac.uk
Z Stamataki
Marcelo Andrade De Lima m.andrade.de.lima@keele.ac.uk
JE Turnbull
Z Yang
E Vicenzi
Mark Skidmore m.a.skidmore@keele.ac.uk
FL Khanim
Alan Richardson a.richardson1@keele.ac.uk
Abstract
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.
Citation
Davies, S., Mycroft-West, C., Pagani, I., Hill, H., Chen, Y.-H., Karlsson, R., Bagdonaite, I., Guimond, S., Stamataki, Z., Andrade De Lima, M., Turnbull, J., Yang, Z., Vicenzi, E., Skidmore, M., Khanim, F., & Richardson, A. (2021). The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models. Frontiers in Pharmacology, 12, 660490. https://doi.org/10.3389/fphar.2021.660490
Journal Article Type | Article |
---|---|
Acceptance Date | Jun 28, 2021 |
Publication Date | Aug 6, 2021 |
Publicly Available Date | May 30, 2023 |
Journal | Frontiers in Pharmacology |
Electronic ISSN | 1663-9812 |
Publisher | Frontiers Media |
Volume | 12 |
Pages | 660490 |
DOI | https://doi.org/10.3389/fphar.2021.660490 |
Keywords | ACE2, COVID-19, SARS-CoV-2, fenofibrate, fibrate |
Public URL | https://keele-repository.worktribe.com/output/420812 |
Publisher URL | https://www.frontiersin.org/articles/10.3389/fphar.2021.660490/full#h13 |
Files
fphar-12-660490.pdf
(2.7 Mb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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