RT Journal Article
SR Electronic
T1 The hyperlipidaemic drug fenofibrate significantly reduces infection by SARS-CoV-2 in cell culture models
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.10.426114
DO 10.1101/2021.01.10.426114
A1 Scott P. Davies
A1 Courtney J. Mycroft-West
A1 Isabel Pagani
A1 Harriet J. Hill
A1 Yen-Hsi Chen
A1 Richard Karlsson
A1 Ieva Bagdonaite
A1 Scott E. Guimond
A1 Zania Stamataki
A1 Marcelo Andrade De Lima
A1 Jeremy E. Turnbull
A1 Zhang Yang
A1 Elisa Vicenzi
A1 Mark A. Skidmore
A1 Farhat Khanim
A1 Alan Richardson
YR 2021
UL http://biorxiv.org/content/early/2021/01/19/2021.01.10.426114.abstract
AB The 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 dimerization of 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 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, these studies identify fenofibrate as a potential therapeutic agent requiring urgent clinical evaluation to treat SARS-CoV-2 infection.Teaser The approved drug fenofibrate inhibits infection by SARS-COV-2Competing Interest StatementThe authors have declared no competing interest.AbbreviationsCsssteady-state plasma concentrationCmaxmaximum plasma concentrationLgBITLarge binary interaction technologyHiBITHigh affinity binary interaction technologyRBDReceptor binding domainACE2Angiotensin converting enzyme 2SARSSevere acute respiratory syndromeELISAEnzyme-linked immunosorbent assay