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.

Automated summary

Coronaviruses use their spike proteins to interact with protein or carbohydrate receptors and infect cells. Three known protein receptors, ANPEP/CD13, DPP IV/CD26, and ACE2, play important roles in the infection of human coronaviruses. These receptors are involved in various physiological processes and expressed in different tissues/cell types. Understanding the commonalities and functions of these enzymes, as well as their impact on systemic deregulations and multi-organ failures, is crucial for developing effective medications against coronaviruses.