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

Background: 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. Methods: 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. Results: ORF7a activates and promotes G2/M phase transition via cyclin-related enzymatic activity domains. Conclusion: 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.