Olive Leaf Extract Downregulates the Protein Expression of Key SARS-CoV-2 Entry Enzyme ACE-2, TMPRSS2, and Furin

Chem Biodivers. 2024 Aug;21(8):e202400717. doi: 10.1002/cbdv.202400717. Epub 2024 Jul 26.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses ongoing global health challenges due to its propensity for mutations, which can undermine vaccine efficacy. With no definitive treatment available, urgent research into affordable and biocompatible therapeutic agents is extremely urgent. Angiotensin converting enzyme-2 (ACE-2), transmembrane protease serine subtype 2 (TMPRSS2), and Furin enzymes, which allow the virus to enter cells, are particularly important as potential drug targets among scientists. Olive leaf extract (OLE) has garnered attention for its potential against Coronavirus Disease-9 (COVID-19), yet its mechanism remains understudied. In this study, we aimed to investigate the effects of OLE on ACE-2, TMPRSS2, and Furin protein expressions by cell culture study. Total phenol, flavonoid content, and antioxidant capacity were measured by photometric methods, and oleuropein levels were measured by liquid LC-HR-MS. Cell viability was analyzed by ATP levels using a luminometric method. ACE-2, TMPRSS2, and Furin expressions were analyzed by the Western Blotting method. ACE-2, TMPRSS2, and Furin protein expression levels were significantly lower in a dose dependent manner and the highest inhibition was seen at 100 μg/ml OLE. The results showed that OLE may be a promising treatment candidate for COVID-19 disease. However, further studies need to be conducted in cells co-infected with the virus.

Keywords: Furin; Severe acute respiratory syndrome coronavirus 2; angiotensin converting enzyme-2; olive leaf extract; transmembrane protease serine subtype 2.

MeSH terms

  • Angiotensin-Converting Enzyme 2* / genetics
  • Angiotensin-Converting Enzyme 2* / metabolism
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Cell Survival / drug effects
  • Down-Regulation / drug effects
  • Furin* / antagonists & inhibitors
  • Furin* / metabolism
  • Humans
  • Olea* / chemistry
  • Plant Extracts* / chemistry
  • Plant Extracts* / pharmacology
  • Plant Leaves* / chemistry
  • SARS-CoV-2* / drug effects
  • Serine Endopeptidases* / metabolism
  • Virus Internalization / drug effects

Substances

  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • Furin
  • TMPRSS2 protein, human
  • ACE2 protein, human
  • Plant Extracts
  • FURIN protein, human
  • Antiviral Agents