Human Coronavirus Cell Receptors Provide Challenging Therapeutic Targets.

Coronaviruses interact with protein or carbohydrate receptors through their spike proteins to infect cells. Even if the known protein receptors for these viruses have no evolutionary relationships, they do share ontological commonalities that the virus might leverage to exacerbate the pathophysiology. ANPEP/CD13, DPP IV/CD26, and ACE2 are the three protein receptors that are known to be exploited by several human coronaviruses. These receptors are moonlighting enzymes involved in several physiological processes such as digestion, metabolism, and blood pressure regulation; moreover, the three proteins are expressed in kidney, intestine, endothelium, and other tissues/cell types. Here, we spot the commonalities between the three enzymes, the physiological functions of the enzymes are outlined, and how blocking either enzyme results in systemic deregulations and multi-organ failures via viral infection or therapeutic interventions is addressed. It can be difficult to pinpoint any coronavirus as the target when creating a medication to fight them, due to the multiple processes that receptors are linked to and their extensive expression.

Comprehensive Oncogenic Features of Coronavirus Receptors in Glioblastoma Multiforme.

The COVID-19 pandemic caused by SARS-CoV-2 infection has placed health systems under excessive pressure and especially elderly people with cancer. Glioblastoma multiforme (GBM) is a malignant brain tumor with an increasing incidence in elderly individuals, and thereby GBM patients are a vulnerable population during the COVID-19 outbreak. Accumulating studies have implied that SARS-CoV-2 might invade the brain directly via coronavirus receptors. However, little is known about SARS-CoV-2 infection in the clinical development of GBM. Here, we explored the oncogenic roles of six coronavirus receptors (ACE2, DPP4, ANPEP, AXL, TMPRSS2, and ENPEP) in GBM using bioinformatics and experimental approaches. We found that ANPEP and ENPEP were significantly increased at both the mRNA and protein levels in GBM compared with normal brain tissue. Kaplan-Meier survival curves and Cox regression analysis demonstrated that high expressions of ANPEP and ENPEP are associated with poor prognosis and survival. Moreover, all receptors are positively correlated with the immune infiltration levels of monocyte. Furthermore, we identified 245 genes between COVID-19 and coronavirus receptors-correlated genes in GBM and performed a thorough analysis of their protein-protein interaction network, functional signaling pathway and molecular process. Our work explores for the first time the association of coronavirus receptors with GBM and suggests ANPEP and ENPEP as potential therapeutic targets of GBM irrespective of COVID-19.

In vitro analysis of the renin-angiotensin system and inflammatory gene transcripts in human bronchial epithelial cells after infection with severe acute respiratory syndrome coronavirus.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus family member that triggers a respiratory disease similar to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are very similar to each other in many respects, such as structure, genetics, and pathobiology. We hypothesized that coronaviruses could affect pulmonary tissues via integration with the critical immune genes after their interaction with renin-angiotensin system (RAS) elements. The aim of the present bioinformatics study was to assess expression changes of the RAS and non-RAS genes, particularly immune response genes, in the lung epithelial cells after infection with SARS-CoV. METHODS: Linear regression, hierarchical clustering, pathway analysis, and network analysis were performed using the E-GEOD-17400 data set. RESULTS: The whole-genome expression data of the lung epithelial cells infected with SARS-CoV for 12, 24, and 48 hours were analyzed, and a total of 15 RAS family and 29 immune genes were found to be highly correlated with the exposure time to the virus in the studied groups. CONCLUSION: RAS genes are important at the initiation of the infections caused by coronavirus family members and may have a strong relationship with the exchange of immune genes in due course following the infection.