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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Article number660490
Number of pages15
JournalFrontiers in Pharmacology
Volume12
DOIs
Publication statusPublished - 6 Aug 2021

Bibliographical note

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

Keywords

  • fenofibrate
  • fibrate
  • SARS-CoV-2
  • COVID-19
  • ACE2

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