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

Med Hypotheses. 2020 Oct;143:110197. doi: 10.1016/j.mehy.2020.110197. Epub 2020 Aug 17.


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.

Keywords: COVID-19; Endothelium; Exercise; PPARα; Vascular.

MeSH terms

  • Betacoronavirus
  • COVID-19
  • COVID-19 Drug Treatment
  • Comorbidity
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / therapy*
  • Cytoplasm / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Exercise
  • Exercise Therapy / methods*
  • Fenofibrate / chemistry
  • Humans
  • Inflammation
  • Lipid Metabolism
  • Lipoylation
  • Lung / metabolism
  • Obesity / complications
  • PPAR alpha / metabolism*
  • Pandemics
  • Pneumonia, Viral / therapy*
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / metabolism*


  • PPAR alpha
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Fenofibrate