COVID-19: ABC System and LBP-like Function of ORF7a Activate Monocytes to Induce Diabetes

Abstract

Diabetes and obesity are important factors that make COVID-19 worse. Lipopolysaccharide activates the natural immune system response in obese and diabetic patients' adipose tissue and increases the risk of susceptibility and severity of COVID-19. In this study, bioinformatics techniques such as domain search and molecular docking were used to study the relationship between the ORF7a protein of the SARS-COV-2 virus and lipopolysaccharide. The results show that the transmembrane protein ORF7a has ABC transporter domains: ATP binding and ABC transmembrane domains. The ABC transport domain of ORF7a transported molecules such as metal ions, heme, nucleosides, amino acids, oligopeptides, sugars, vitamins, salts, alkalis etc.. Moreover, it had a multi-drug efflux function. ORF7a also has lipopolysaccharide synthesized domains. It bound the lipopolysaccharide synthesized by ORF7a to CD14 molecule through lipopolysaccharide-binding protein (LBP) to activate CD14 + monocytes. The extracellular ORF7a with the N-terminus and C-terminus cut off still has the BPI11/LBP domain ("CELYHYQECVR") and two ATP-binding motifs ("HYQEC" and "TYEGNS"). The extracellular ORF7a had a similar function of LBP, binding and activating CD14 + monocytes with the help of two ATP-binding structures. We speculated that cells infected by the SARS-COV-2 virus often used its surface lipopolysaccharides to build expanded barriers to resist T cells, NK cells, and drugs. More lipopolysaccharides also activated CD14 + monocytes to release various inflammatory factors, damaging adipose and vascular endothelial tissue to induce diabetes and hypertension.