Davies, SP, Mycroft-West, CJ, Pagani, I, Hill, HJ, Chen, Y-H, Karlsson, R, Bagdonaite, I, Guimond, SE, Stamataki, Z, de Lima, MA, Turnbull, JE, Yang, Z, Vicenzi, E, Skidmore, MA, Khanim, FL and Richardson, A (2021) The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models. Frontiers in Pharmacology, 12. ISSN 1663-9812

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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.

Item Type: Article
Additional Information: © 2021 Davies, Mycroft-West, Pagani, Hill, Chen, Karlsson, Bagdonaite, Guimond, Stamataki, De Lima, Turnbull, Yang, Vicenzi, Skidmore, Khanim and Richardson. 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.
Uncontrolled Keywords: fenofibrate, fibrate, SARS-CoV-2, COVID-19, ACE2
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history
R Medicine > R Medicine (General)
Divisions: Faculty of Natural Sciences > School of Life Sciences
Depositing User: Symplectic
Date Deposited: 25 Aug 2021 13:17
Last Modified: 24 Nov 2021 10:10
URI: https://eprints.keele.ac.uk/id/eprint/9929

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