Affiliation:
1. School of Computer Science and Engineering, Sichuan University of Science & Engineering, Zigong, 643002, China
2. School of Life Science and Food Engineering, Yibin University, Yibin, 644000, China
Abstract
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.
Funder
Zigong City Key Science and Technology Plan Project
Talent Introduction Project of Sichuan University of Science and Engineering
Publisher
Bentham Science Publishers Ltd.
Subject
Molecular Biology,Biochemistry