期刊
FRONTIERS IN PHARMACOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.660490
关键词
fenofibrate; fibrate; SARS-CoV-2; COVID-19; ACE2
资金
- Keele University
- University of Birmingham
- MRF intermediate career fellowship (UKRI) [MRF-1690001-F-STAM-C0826]
- BBSRC [BB/LO23717/1, BIV-HVB-2020/07/SKIDMORE, BB/S009787/1]
- Bando, Italian Ministry of Health [COVID-2020-12371617]
- Danish National Research Foundation [DNRF107]
- Lundbeck Foundation
- GlycoSkin H2020-ERC [GAP-772735]
- European Commission (GlycoImaging) [H2020-MSCA-ITN-721297]
- Innovation Fund Denmark
- University of Liverpool
- BBSRC [BB/S009787/1] Funding Source: UKRI
The study suggests that fenofibrate and fenofibric acid may be effective in reducing SARS-CoV-2 infection by up to 70% at clinically achievable concentrations. These drugs have a history of clinical use and relatively good safety profiles, making them potential therapeutic agents that require urgent clinical evaluation for treating SARS-CoV-2 infection.
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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