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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

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


Authors

SP Davies

CJ Mycroft-West

I Pagani

HJ Hill

Y-H Chen

R Karlsson

I Bagdonaite

Z Stamataki

JE Turnbull

Z Yang

E Vicenzi

FL Khanim



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.

Journal Article Type Article
Acceptance Date Jun 28, 2021
Publication Date Aug 6, 2021
Publicly Available Date May 30, 2023
Journal Frontiers in Pharmacology
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
Publisher URL https://www.frontiersin.org/articles/10.3389/fphar.2021.660490/full#h13

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