Coronavirus disease 2019 (COVID-19), human erythrocytes and the PKC-alpha/-beta inhibitor chelerythrine -possible therapeutic implication

Cell Cycle. 2020 Dec;19(24):3399-3405. doi: 10.1080/15384101.2020.1859197. Epub 2020 Dec 11.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. Until now, diverse drugs have been used for the treatment of COVID-19. These drugs are associated with severe side effects, e.g. induction of erythrocyte death, named eryptosis. This massively affects the oxygen (O2) supply of the organism. Therefore, three elementary aspects should be considered simultaneously: (1) a potential drug should directly attack the virus, (2) eliminate virus-infected host cells and (3) preserve erythrocyte survival and functionality. It is known that PKC-α inhibition enhances the vitality of human erythrocytes, while it dose-dependently activates the apoptosis machinery in nucleated cells. Thus, the use of chelerythrine as a specific PKC-alpha and -beta (PKC-α/-β) inhibitor should be a promising approach to treat people infected with SARS-CoV-2.

Keywords: RNA polymerases; SARS-CoV-2; chelerythrine; erythrocytes; mammalian target of rapamycin complex 1 & 2 (mTORC1/-2); protein kinase C-alpha (PKC-α).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Apoptosis / drug effects
  • Benzophenanthridines / adverse effects
  • Benzophenanthridines / pharmacology*
  • Benzophenanthridines / therapeutic use
  • COVID-19 / immunology
  • COVID-19 / metabolism
  • COVID-19 Drug Treatment*
  • DNA-Directed RNA Polymerases / metabolism
  • Erythrocytes / drug effects
  • Erythrocytes / immunology*
  • Erythrocytes / metabolism
  • Humans
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Mechanistic Target of Rapamycin Complex 2 / metabolism
  • Protein Biosynthesis / drug effects
  • Protein Kinase C beta / antagonists & inhibitors*
  • Protein Kinase C-alpha / antagonists & inhibitors*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • RNA Viruses / genetics
  • RNA Viruses / metabolism
  • Respiratory Tract Diseases / enzymology
  • Respiratory Tract Diseases / metabolism
  • Respiratory Tract Diseases / virology*

Substances

  • Antiviral Agents
  • Benzophenanthridines
  • Protein Kinase Inhibitors
  • chelerythrine
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Protein Kinase C beta
  • Protein Kinase C-alpha
  • DNA-Directed RNA Polymerases

Grants and funding

This work was financed by Mehrdad Ghashghaeinia.