The cholesterol-lowering drug fenofibrate significantly reduces cellular infection by SARS-CoV-2.

Key Messages

In this lab study, 100 approved drugs were screened to identify any anti SARS-CoV-2 effects. Fenofibrate ranked as the most effective antiviral agent.

The analysis of the infected cells and molecular binding assays showed that treating cells with fenofibrate reduced SARS-CoV-2 infection by up to 70%, compared to cells not treated with the drug.

Two mechanisms of action of fenofibrate against SARS-CoV-2 were identified.

Fenofibrate blocks viral infection by 1) interacting with the SARS-CoV-2 spike protein to prevent it from binding to ACE2, the cell surface protein the virus uses to enter the cell and 2) also altering the conformation of the ACE2 protein so the virus can no longer recognize it.

Frontiers in Pharmacology

Publication Date: August 6, 2021
Peer Reviewed: Yes
Publication Type: Original | Preclinical
DOI: https://www.doi.org/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

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.