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

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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
Number of pages	15
Journal	Frontiers in Pharmacology
Volume	12
DOIs	https://doi.org/10.3389/fphar.2021.660490
Publication status	Published - 6 Aug 2021

Bibliographical note

Keywords

fenofibrate
fibrate
SARS-CoV-2
COVID-19
ACE2

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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, Article 660490. https://doi.org/10.3389/fphar.2021.660490

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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.",

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author = "Davies, {Scott P} and Mycroft-West, {Courtney J} and Isabel Pagani and Hill, {Harriet J} and Yen-Hsi Chen 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 = "Copyright {\textcopyright} 2021 Davies, Mycroft-West, Pagani, Hill, Chen, Karlsson, Bagdonaite, Guimond, Stamataki, De Lima, Turnbull, Yang, Vicenzi, Skidmore, Khanim and Richardson.",

year = "2021",

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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 & 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

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AU - Davies, Scott P

AU - Mycroft-West, Courtney J

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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

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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 - fenofibrate

KW - fibrate

KW - SARS-CoV-2

KW - COVID-19

KW - ACE2

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DO - 10.3389/fphar.2021.660490

M3 - Article

C2 - 34421587

SN - 1663-9812

VL - 12

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

M1 - 660490

ER -

The hyperlipidaemic drug fenofibrate significantly reduces infection by SARS-CoV-2 in cell culture models

Abstract

Bibliographical note

Keywords

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