Conclusion
From the structural point of view ACE2 is closely related to ACE, and its discovery was a by-product of ACE investigations. However, this macromolecule has soon showed peculiar functional properties and has attracted increasing attention. The expression of ACE2 in the heart, kidney and vascular system pointed to a role in the regulation of blood pressure and cardiovascular homeostasis, possibly as a counterbalance to ACE activation, but this hypothesis now appears to be too simplistic. Additional functions of ACE2 are strongly suggested by its capability to modulate cytokine metabolism and the inflammatory reaction, as well as by its remarkable expression in the respiratory tract.
The recent COVID-19 pandemic has put ACE2 in the spotlight, since it has been identified as the initial target of the SARS-Cov and SARS-Cov2 viruses, representing the receptor responsible for cellular adhesion. Recent investigations have clarified the molecular details of the interaction of ACE2 with the spike glycoprotein present in this class of coronaviruses, and have partly unraveled the mechanism of protein cleavage and cellular entry. ACE2 density on cell surface and ACE2-modulated inflammatory reactions have been suggested to be important determinants of COVID-19 susceptibility and clinical course, while drugs interfering with ACE2 expression, availability and processing are under investigation as potential therapeutic agents. However, several crucial issues concerning the link between ACE2 and COVID-19 pathophysiology are still unclear, pointing to the need for focused experimental investigations and prospective clinical trials.