Immune interaction map of human SARS-CoV-2 target proteins: implications for therapeutic avenues

Abstract

Background There exists increasing evidence that people with preceding medical conditions, such as asthma, diabetes, cancers and heart disease, have a higher risk of infection with SARS-CoV-2 and are more vulnerable to severe disease.Methods To get insights into the role of the immune system upon COVID-19 infection, 2811 genes of the gene ontology term “immune system process GO: 0002376” were selected for analyses. The immune system genes potentially co-expressed with the human targets of SARS-CoV-2 (HT-SARS-CoV-2) ACE2, TMPRSS2 and FURIN were determined in tissue samples from patients with cancer and diabetes mellitus. The network between HT-SARS-CoV-2 and immune system process genes was analyzed based on functional protein associations using STRING. In addition, STITCH was employed to determine druggable targets.Results DPP4 was the only immune system process gene, which was coexpressed with the three HT-SARS-CoV-2 genes, while eight other immune genes were at least co-expressed with two HT-SARS-CoV-2 genes. STRING analysis between immune and HT-SARS-CoV-2 genes plotted 19 associations of 8 commonly networking genes in mixed healthy (323) and cancer (11003) tissues in addition to normal (87), cancer (90) and diabetic (128) pancreatic tissues. Using this approach, three druggable connections between HT-SARS-CoV-2 and immune system process genes were identified. They include positive associations of ACE2 - DPP4 and TMPRSS2 – SRC as well as a negative association of FURIN with ADAM17. Furthermore, the 16 drugs were extracted from STITCH (score <0.8) with 32 target genes.Conclusions This bioinformatics pipeline identified for the first time an immunological network associated with COVID-19 infection thereby postulating novel therapeutic opportunities.