Hypertension. 2020 Aug 27. doi: 10.1161/HYPERTENSIONAHA.120.15256. Online ahead of print.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) originated from Wuhan, China in December 2019, and rapidly spread to other areas worldwide. Since then, COVID-19 has reached pandemic proportions with more than 570,000 deaths globally by mid-July 2020. The magnitude of the outbreak and the potentially severe clinical course of COVID-19 has led to a burst of scientific research on this novel coronavirus and its host receptor, angiotensin converting enzyme-2 (ACE2). ACE2 is a homolog of the angiotensin-I converting enzyme (ACE) that acts on several substrates in the renin-angiotensin system. With unprecedented speed, scientific research has solved the structure of SARS-CoV-2 and imaged its binding with the ACE2 receptor. In SARS-CoV-2 infection, the viral spike (S) protein receptor binding domain (RBD) binds to ACE2 to enter the host cell. ACE2 expression in the lungs is relatively low, but it is present in type II pneumocytes, a cell type also endowed with transmembrane protease serine 2 (TMPRSS2). This protease is critical for priming the SARS-CoV-2 S protein to complex with ACE2 and enter the cells. Herein, we review the current understanding of the interaction of SARS-CoV-2 with ACE2 as it has rapidly unfolded over the last months. While it should not be assumed that we have a complete picture of SARS-CoV-2's mechanism of infection and its interaction with ACE2 much has been learned with clear therapeutic implications. Potential therapies aimed at intercepting SARS-CoV-2 from reaching the full-length membrane-bound ACE2 receptor using soluble ACE2 protein and other potential approaches are briefly discussed as well.