Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Nov;71(10-11):1159-1167.
doi: 10.1007/s00011-022-01615-w. Epub 2022 Aug 8.

Fenofibrate for COVID-19 and related complications as an approach to improve treatment outcomes: the missed key for Holy Grail

Shadi Salem Alkhayyat  1 , Hayder M Al-Kuraishy  2 , Ali I Al-Gareeb  2 , Maisra M El-Bouseary  3 , Amal M AboKamer  4 , Gaber El-Saber Batiha  5 , Jesus Simal-Gandara  6
Affiliations
Review

Fenofibrate for COVID-19 and related complications as an approach to improve treatment outcomes: the missed key for Holy Grail

Shadi Salem Alkhayyat et al. Inflamm Res. 2022 Nov.

Abstract

Introduction: Fenofibrate is an agonist of peroxisome proliferator activated receptor alpha (PPAR-α), that possesses anti-inflammatory, antioxidant, and anti-thrombotic properties. Fenofibrate is effective against a variety of viral infections and different inflammatory disorders. Therefore, the aim of critical review was to overview the potential role of fenofibrate in the pathogenesis of SARS-CoV-2 and related complications.

Results: By destabilizing SARS-CoV-2 spike protein and preventing it from binding angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 entry, fenofibrate can reduce SARS-CoV-2 entry in human cells Fenofibrate also suppresses inflammatory signaling pathways, which decreases SARS-CoV-2 infection-related inflammatory alterations. In conclusion, fenofibrate anti-inflammatory, antioxidant, and antithrombotic capabilities may help to minimize the inflammatory and thrombotic consequences associated with SARSCoV-2 infection. Through attenuating the interaction between SARS-CoV-2 and ACE2, fenofibrate can directly reduce the risk of SARS-CoV-2 infection.

Conclusions: As a result, fenofibrate could be a potential treatment approach for COVID-19 control.

Keywords: Angiotensin-converting enzyme 2; COVID-19; Fenofibrate; SARS-CoV-2.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Chemical structure of fenofibrate
Fig. 2
Fig. 2
Anti-inflammatory effects of fenofibrate: fenofibrate, through activation of peroxisome proliferator-activated receptor alpha (PPAR-α), inhibits inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), matrix metalloproteinase 9 (MMP9), and activates release of adiponectin and inhibitory kappa B (IκB), causing a reduction of inflammatory disorders
Fig. 3
Fig. 3
Mechanism of fenofibrate against SARS-CoV-2 infection: SARS-CoV-2 induces activation of signaling pathways including toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), mechanistic target of rapamycin (mTOR), nod-like receptor pyrin 3 (NLRP3) inflammasome, advanced glycation end product (AGE), p38 mitogen-activated protein kinase (p38MAPK), and vascular endothelial growth factor (VEGF) with subsequent development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)
See this image and copyright information in PMC

References

    1. Rasheed HA, Hussien NR, Al-Naimi MS, Al-Kuraishy HM, Al-Gareeb AI. Fenofibrate and Crataegus oxyacantha is an effectual combo for mixed dyslipidemia. Biomed Biotechnol Res J. 2020;4(3):259. doi: 10.4103/bbrj.bbrj_26_20. - DOI
    1. Goncalves MD, Hwang SK, Pauli C, Murphy CJ, Cheng Z, Hopkins BD, et al. Fenofibrate prevents skeletal muscle loss in mice with lung cancer. Proc Natl Acad Sci USA. 2018;115(4):E743–E752. doi: 10.1073/pnas.1714703115. - DOI - PMC - PubMed
    1. Jung JY, Choi Y, Suh CH, Yoon D, Kim HA. Effect of fenofibrate on uric acid level in patients with gout. SciRep. 2018;8(1):16767. doi: 10.1038/s41598-018-35175-z. - DOI - PMC - PubMed
    1. FIELD Study Investigators Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366(9500):1849–1861. doi: 10.1016/S0140-6736(05)67667-2. - DOI - PubMed
    1. Fischer J, Ganellin CR. Analogue-based drug discovery. Chem Int—Newsmag IUPAC. 2010;32(4):12–15.

Grants and funding