Frontiers in Pharmacology (Aug 2021)

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,
  • Jeremy E. Turnbull,
  • Zhang Yang,
  • Elisa Vicenzi,
  • Mark A. Skidmore,
  • Farhat L. Khanim,
  • Alan Richardson

DOI
https://doi.org/10.3389/fphar.2021.660490
Journal volume & issue
Vol. 12

Abstract

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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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