Usage of peptidases by SARS-CoV-2 and several human coronaviruses as receptors: A mysterious story

Coronaviruses recognize a variety of host receptors to infect many humans and animals. Newly emerged severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) recognizes angiotensin-converting enzyme 2 (ACE2) to gain entry into different cells. Interestingly, besides SARS-CoV2, four other human coronaviruses (HCoVs) use three different ectopeptidases (ACE2, dipeptidyl peptidase 4, and aminopeptidase N) as receptors independent of their common peptidase activity. This issue has led to the important question why do several HCoVs rely on peptidases as their receptors?. In this paper, we discussed to answer this question. Mostly, it seems that the use of peptidases by HCoVs may be more related to their widespread presence on target cells and also viruses prefer to take advantage of molecules with relatively low affinity for their natural ligands through evolving a stronger binding affinity to the surface receptors for entry and endocytosis. Meanwhile evolutionary conservation of these receptors may allow HCoVs to switch between different host species. Finally, the choice of peptidases by HCoVs may reflect the trial and error nature of evolution. In conclusion, substantial efforts are needed to get a strong picture of this fascinating question and poorly explored area. Detailed understanding of the entry mechanisms offers opportunities for the development of refined strategies to stop viruses.

Automated summary

Coronaviruses, including SARS-CoV-2, use various host receptors for cell entry. The choice of peptidases as receptors by some HCoVs may be related to their widespread presence on target cells and the viruses' preference for molecules with relatively low affinity as well as evolutionary conservation of these receptors allowing the viruses to switch between host species. Additionally, this selection process may reflect the trial and error nature of evolution.