ORF7a Palsies Macrophage to Worsen Diabetes by SMB/BPI/ABC Domains and PARP/Cap/Cyclin Enzyme System

Abstract

Such factors as diabetes and obesity can dramatically worsen COVID-19 symptoms. In addition, macrophage accumulation in adipose tissue is related to obesity. Therefore, macrophages play a significant role in raising COVID-19 susceptibility and severity in diabetes and obese patients. 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, the functional impact of SARS-CoV-2 ORF7a on macrophages was analyzed using a domain-searching bioinformatics technique. Ca2+ binding domain, kinase and phosphatase, SMB/SRCR, LBP/BPI/CETP, ABC, TIR,PARP, Flavivirus Cap enzyme, Cyclin, and other domains have been identified in SARS-CoV-2 ORF7a. ORF7a binds to oxidized low-density lipoprotein cholesterol particles by the macrophage receptor-like domains such as SMB/SRCR and enters macrophages via macropinocytosis. Then, ORF7a prevents 18 S rRNA maturation and adds flavivirus cap 0/1/2 to mRNA to interfere with transcription and translation via PARP, Flavivirus Cap enzyme, and other associated domains. Meanwhile, ORF7a activates and promotes G2/M phase transition via cyclin-related enzymatic activity domains. The destructive activity of ORF7a hijacks the nitric oxide release pathway of macrophages and promotes macrophage death, enabling the virus to elude the innate immune system and aggravate diabetes-related problems in patients. 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.