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

doi:10.3389/fphar.2021.660490

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

SP Davies

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