Fig. 1. SARS-CoV-2-induced alterations in glucose metabolism.

In mammalian cells, SARS-CoV-2 shifts cellular metabolism from oxidative phosphorylation to glycolysis, which results in a decrease in ATP generation. The key rate-limiting enzymes in glycolysis, including PKM2 and HK2, were upregulated in COVID-19. The decreased PDC can lead to an uncoupling between glycolysis and TCA, which would induce intracellular acidosis and energy depletion. Under an anaerobic condition in COVID-19, the depletion of GSH from the pentose phosphate pathway’s blockage could cause oxidative damage by SARS-CoV-2. The new virus elevates the hexosamine biosynthetic pathway, which would result in massive amounts of IRF5. IRF5 involves worsening pro-inflammatory pathways that ultimately lead to hyper inflammation, a cytokine storm, and multiorgan failure. GSH, glutathione; HK2, hexokinase 2; IRF5, interferon regulatory factor-5; LDH, lactate dehydrogenase; NADPH, nicotinamide adenine dinucleotide phosphate; PDC, pyruvate dehydrogenase complex; PEP, phosphoenolpyruvate; PDK, pyruvate dehydrogenase kinase; PKM2, pyruvate kinase isozyme M2; TCA, tricarboxylic acid