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.
Highlights
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for a pandemic, which has cost over 1.9 million lives worldwide so far (Dhama et al, 2020; World Health Organization, 2020; Wu et al, 2020)
While vaccine programs will hopefully reduce infection rates and virus spread in the longer term, there is still an urgent need to expand our arsenal of drugs to treat severe acute respiratory syndrome (SARS)-CoV-2-positive patients
We have identified that the off-patent licensed drug fenofibrate has the potential to treat SARS-CoV-2 infections
Summary
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for a pandemic, which has cost over 1.9 million lives worldwide so far (Dhama et al, 2020; World Health Organization, 2020; Wu et al, 2020). The emergence of new virus variants with higher transmissibility rates is seeing rapid increases in infection rates and deaths across the world. While the clinical data are very promising, the vaccines are not recommended or suitable in all patient groups, e.g., children, those with hyperimmune disorders, and those using immunosuppressants (Meo et al, 2021), and with the global spread of viral variants of concern, e.g., Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2, it is presently unclear whether the current vaccines will offer sufficient protection to emerging strains (Meo et al, 2021). While vaccination has been shown to reduce infection rates and severity of disease, we are as yet unsure of the strength and duration of the response. Therapies are still urgently needed to manage COVID-19 patients who develop symptoms and/or require hospitalization
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