7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19

J Steroid Biochem Mol Biol. 2021 Sep:212:105939. doi: 10.1016/j.jsbmb.2021.105939. Epub 2021 Jun 9.

Abstract

7-Ketocholesterol, which is one of the earliest cholesterol oxidization products identified, is essentially formed by the auto-oxidation of cholesterol. In the body, 7-ketocholesterol is both provided by food and produced endogenously. This pro-oxidant and pro-inflammatory molecule, which can activate apoptosis and autophagy at high concentrations, is an abundant component of oxidized Low Density Lipoproteins. 7-Ketocholesterol appears to significantly contribute to the development of age-related diseases (cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease), chronic inflammatory bowel diseases and to certain cancers. Recent studies have also shown that 7-ketocholesterol has anti-viral activities, including on SARS-CoV-2, which are, however, lower than those of oxysterols resulting from the oxidation of cholesterol on the side chain. Furthermore, 7-ketocholesterol is increased in the serum of moderately and severely affected COVID-19 patients. In the case of COVID-19, it can be assumed that the antiviral activity of 7-ketocholesterol could be counterbalanced by its toxic effects, including pro-oxidant, pro-inflammatory and pro-coagulant activities that might promote the induction of cell death in alveolar cells. It is therefore suggested that this oxysterol might be involved in the pathophysiology of COVID-19 by contributing to the acute respiratory distress syndrome and promoting a deleterious, even fatal outcome. Thus, 7-ketocholesterol could possibly constitute a lipid biomarker of COVID-19 outcome and counteracting its toxic effects with adjuvant therapies might have beneficial effects in COVID-19 patients.

Keywords: 7-Ketocholesterol; Adjuvant therapies; COVID-19; Oxysterols; SARS-CoV-2; Viral diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Biomarkers / blood
  • COVID-19 / blood
  • COVID-19 / etiology*
  • COVID-19 Drug Treatment
  • Humans
  • Ketocholesterols / blood*
  • Ketocholesterols / metabolism

Substances

  • Antiviral Agents
  • Biomarkers
  • Ketocholesterols
  • 7-ketocholesterol