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

Scott P. Davies; Courtney J. Mycroft-West; Isabel Pagani; Harriet J. Hill; Yen Hsi Chen; Richard Karlsson; Ieva Bagdonaite; Scott E. Guimond; Zania Stamataki; Marcelo Andrade De Lima; Jeremy E. Turnbull; Zhang Yang; Elisa Vicenzi; Mark A. Skidmore; Farhat L. Khanim; Alan Richardson

doi:10.3389/fphar.2021.660490

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

Scott P. Davies, Courtney J. Mycroft-West, Isabel Pagani, Harriet J. Hill, Yen Hsi Chen, Richard Karlsson, Ieva Bagdonaite, Scott E. Guimond, Zania Stamataki, Marcelo Andrade De Lima, Jeremy E. Turnbull, Zhang Yang, Elisa Vicenzi, Mark A. Skidmore, Farhat L. Khanim^*, Alan Richardson

^*Corresponding author for this work

Glycomics Program

Research output: Contribution to journal › Journal article › Research › peer-review

28 Citations (Scopus)

18 Downloads (Pure)

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.

Original language	English
Article number	660490
Journal	Frontiers in Pharmacology
Volume	12
ISSN	1663-9812
DOIs	https://doi.org/10.3389/fphar.2021.660490
Publication status	Published - 2021

Bibliographical note

Publisher Copyright:
© Copyright © 2021 Davies, Mycroft-West, Pagani, Hill, Chen, Karlsson, Bagdonaite, Guimond, Stamataki, De Lima, Turnbull, Yang, Vicenzi, Skidmore, Khanim and Richardson.

Keywords

ACE2
COVID-19
fenofibrate
fibrate
SARS-CoV-2

Access to Document

10.3389/fphar.2021.660490Licence: CC BY

The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture ModelsFinal published version, 2.59 MBLicence: CC BY

Cite this

Davies, S. P., Mycroft-West, C. J., Pagani, I., Hill, H. J., Chen, Y. H., Karlsson, R., Bagdonaite, I., Guimond, S. E., Stamataki, Z., De Lima, M. A., Turnbull, J. E., Yang, Z., Vicenzi, E., Skidmore, M. A., Khanim, F. L., & 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

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

In: Frontiers in Pharmacology, Vol. 12, 660490, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Davies, SP, Mycroft-West, CJ, Pagani, I, Hill, HJ, Chen, YH, Karlsson, R, Bagdonaite, I, Guimond, SE, Stamataki, Z, De Lima, MA, Turnbull, JE , Yang, Z, Vicenzi, E, Skidmore, MA, Khanim, FL & Richardson, A 2021, 'The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models', Frontiers in Pharmacology, vol. 12, 660490. https://doi.org/10.3389/fphar.2021.660490

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. / The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models. In: Frontiers in Pharmacology. 2021 ; Vol. 12.

@article{8a6159140ecd49c0b1f8f9091b341de2,

title = "The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models",

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.",

keywords = "ACE2, COVID-19, fenofibrate, fibrate, SARS-CoV-2",

author = "Davies, {Scott P.} and Mycroft-West, {Courtney J.} and Isabel Pagani and Hill, {Harriet J.} and Chen, {Yen Hsi} and Richard Karlsson and Ieva Bagdonaite and Guimond, {Scott E.} and Zania Stamataki and {De Lima}, {Marcelo Andrade} and Turnbull, {Jeremy E.} and Zhang Yang and Elisa Vicenzi and Skidmore, {Mark A.} and Khanim, {Farhat L.} and Alan Richardson",

note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Davies, Mycroft-West, Pagani, Hill, Chen, Karlsson, Bagdonaite, Guimond, Stamataki, De Lima, Turnbull, Yang, Vicenzi, Skidmore, Khanim and Richardson.",

year = "2021",

doi = "10.3389/fphar.2021.660490",

language = "English",

volume = "12",

journal = "Frontiers in Pharmacology",

issn = "1663-9812",

publisher = "Frontiers Research Foundation",

}

TY - JOUR

T1 - The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models

AU - Davies, Scott P.

AU - Mycroft-West, Courtney J.

AU - Pagani, Isabel

AU - Hill, Harriet J.

AU - Chen, Yen Hsi

AU - Karlsson, Richard

AU - Bagdonaite, Ieva

AU - Guimond, Scott E.

AU - Stamataki, Zania

AU - De Lima, Marcelo Andrade

AU - Turnbull, Jeremy E.

AU - Yang, Zhang

AU - Vicenzi, Elisa

AU - Skidmore, Mark A.

AU - Khanim, Farhat L.

AU - Richardson, Alan

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - ACE2

KW - COVID-19

KW - fenofibrate

KW - fibrate

KW - SARS-CoV-2

U2 - 10.3389/fphar.2021.660490

DO - 10.3389/fphar.2021.660490

M3 - Journal article

C2 - 34421587

AN - SCOPUS:85113199801

VL - 12

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

M1 - 660490

ER -