SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE.

Area of Science:

• Cellular Metabolism
• Immunology
• Virology

Background:

• SARS-CoV-2 (COVID-19) infection induces hyperinflammation, linked to increased mortality.
• This inflammation involves elevated cytokine production and Receptor for Advanced Glycation End products (RAGE) hyperactivity.
• Metabolic reprogramming, particularly glycolysis dysfunction, contributes to inflammation and is implicated in various diseases.

Purpose of the Study:

• To investigate the impact of SARS-CoV-2 proteins on cellular metabolism in lung epithelial cells.
• To determine if SARS-CoV-2 infection alters pyruvate kinase M2 (PKM2) expression and promotes AGE accumulation.
• To evaluate the therapeutic potential of a PKM2 stabilizer in reversing SARS-CoV-2-induced metabolic alterations.

Main Methods:

• Utilized the human lung epithelial cell line BEAS-2B.
• Exposed cells to SARS-CoV-2 proteins to study metabolic reprogramming.
• Assessed changes in pyruvate kinase M2 (PKM2) levels, advanced glycation end product (AGE) accumulation, and senescence.
• Administered the PKM2 stabilizer Tepp-46 to assess its effects on metabolic alterations.

Main Results:

• SARS-CoV-2 proteins reprogrammed cellular metabolism, leading to increased PKM2 expression in BEAS-2B cells.
• This metabolic deregulation promoted the accumulation of AGEs and induced cellular senescence.
• Treatment with Tepp-46 reversed the observed glycolysis alterations and restored normal metabolic function.

Conclusions:

• SARS-CoV-2 infection disrupts cellular glycolysis via PKM2 upregulation, contributing to AGE accumulation and senescence.
• Tepp-46 demonstrates potential in mitigating SARS-CoV-2-induced metabolic dysfunction and inflammation.
• Targeting metabolic pathways, specifically PKM2, presents a promising therapeutic avenue for managing COVID-19-related hyperinflammation.