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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Published in:Frontiers in pharmacology Vol. 12; p. 660490
Main Authors: 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
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 06.08.2021
Subjects:
ACE2
COVID-19
fenofibrate
fibrate
Pharmacology
SARS-CoV-2
COVID-19
ACE2
SARS-CoV-2
fenofibrate
fibrate
ISSN:1663-9812, 1663-9812
Online Access:Get full text
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Summary: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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Edited by:Lei Xi, Virginia Commonwealth University, United States
Reviewed by:Kirill Gorshkov, National Center for Advancing Translational Sciences (NCATS), United States
Maria Cristina Albertini, University of Urbino Carlo Bo, Italy
This article was submitted to Translational Pharmacology, a section of the journal Frontiers in Pharmacology
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2021.660490