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

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 (O 2 ) 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.

Therapeutic potential of chelerythrine as a multi-purpose adjuvant for the treatment of COVID-19

“…In the case of respiratory viral infection, protein kinase C activation facilitates nuclear transport of the viral ribonucleoproteins in the infected cells and their subsequent budding at the cell membrane. Hence, protein kinase C is an ideal choice for drug targeting and chelerythrine as an inhibitor of protein kinase C-α/-β mediated viral genome transport would be of a great importance in the induction of apoptosis in the SARS-CoV-2 infected cells [ 16 ].…”

“…Suppression or inhibition of PKC has protective role in erypthosis and prevention of nuclear transport of the viral ribonucleoproteins in infected cells and also dysregulation of the viral replication. [ 11 , 12 , 16 , 48 ] Anti-inflammatory activity Proper inhibition of the body’s inflammatory response in patients with COVID-19 is crucial in the treatment. Chelerythrine has anti-inflammatory activity and can exert this effect by different mechanisms.…”

Phenylethanoid glycosides as a possible COVID-19 protease inhibitor: a virtual screening approach

“…A recent study reported that protein kinase C alpha and beta inhibitors have a pro-apoptotic effect in nucleated cells, and this creates a hostile environment for intracellular parasites including viruses. This can enhance the antiviral activity of antivirus drugs [37]. The dual activity (kinase/ protease) of PGs could make them very promising as anti-COVID-19 agents.…”

COVID-19 induces proatherogenic alterations in moderate to severe non-comorbid patients: A single-center observational study

“…Given the aforementioned results, we next hypothesized that inflammatory and lipid alterations experienced by COVID-19 severe patients would be affecting hematological parameters such as erythrocytes and hemoglobin, the most important players in oxygen and carbon dioxide transportation between the lungs and tissues which is strongly compromised in ICU patients. Erythrocytes also display an important role in immune mechanisms against SARS-CoV-2 infection capturing the virus through gangliosides and sialoglycoprotein glycophorin A (GPA) that act as receptors and deliver to macrophages for elimination [47] . Decreased hemoglobin concentration and erythrocyte number were observed in serum samples of G3 patients independently of T2DM or obesity preexistence.…”