Exercise as medicine for COVID-19: On PPAR with emerging pharmacotherapy.

Key Messages

By comparing exercise with fenofibrate, this article explored the hypothesis that both exercise and fenofibrate work via the PPAR pathway, to help patients manage and recover from COVID-19.

The PPAR pathway affects various biological processes, including cholesterol and glucose metabolism, and overall energy homeostasis. Cholesterol accumulation is known to be required for SARS-CoV-2 replication.

Studies show that the cholesterol-lowering drug fenofibrate inhibits viral replication. It also has anti-inflammatory properties and it can prevent acute injury to the lungs by improving fatty acid oxidation, which is used for energy.

Fenofibrate, together with exercise, could be a promising treatment approach to fight COVID-19.

Medical Hypotheses

Publication Date: August 17, 2020
Peer Reviewed: Yes
Publication Type: Original | Theoretical
DOI: https://www.doi.org/10.1016/j.mehy.2020.110197

Exercise as medicine for COVID-19: On PPAR with emerging pharmacotherapy

Kevin S. Heffernan, Sushant M. Ranadive, Sae Young Jae


Coronavirus disease 2019 (COVID-19) may have a metabolic origin given strong links with risk factors such as lipids and glucose and co-morbidities such as obesity and type 2 diabetes mellitus. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein mediates viral cellular entry via the ACE2 receptor. The cytoplasmic tail of this spike protein is heavily palmitoylated. Emerging studies suggest that SARS-CoV-2 alters lipid metabolism in the lung epithelial cells by modulating peroxisome proliferator-activated receptor alpha (PPARα), possibly contributing to lipotoxicity, inflammation and untoward respiratory effects. Disruption of this process may affect palmitoylation of SARS-CoV spike protein and thus infectivity and viral assembly. COVID-19 is also increasingly being recognized as a vascular disease, with several studies noting prominent systemic endothelial dysfunction. The pathogenesis of endothelial dysfunction may also be linked to COVID-19-mediated metabolic and inflammatory effects. Herein, exercise will be compared to fenofibrate as a possible therapeutic strategy to bolster resilience against (and help manage recovery from) COVID-19. This paper will explore the hypothesis that exercise may be a useful adjuvant in a setting of COVID-19 management/rehabilitation due to its effects on PPARα and vascular endothelial function.