Interaction of SARS-CoV-2 and Other Coronavirus With ACE (Angiotensin-Converting Enzyme)-2 as Their Main Receptor

Abstract

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.

Phytochemicals as Therapeutics Against COVID-19: An In-Silico Study

“…The presence of ACE2 in such tissue confirms the risk of heart attack, kidney damage of the person suffering from COVID-19(Davidson et al 2020). …”

“…This protease is used as priming the S-protein-ACE2 complex formation. The S-protein is composed of few peptide subunits which mediates viral entry via ectodomain, which consists of 3 S1 subunit heads responsible for receptor binding and a trimeric S2 subunit facilitates the membrane fusion (Davidson et al 2020, Ho et al 2006.…”

Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury

“…Soluble ACE2 may act as a competitive interceptor of SARS-CoV-2 by preventing binding of the viral particle to surface-bound, full-length ACE2. Recently, nasal spray application [ 363 ] or systemic administration [ 330 ] of soluble ACE2 has been suggested for the treatment of COVID-19. Since plasma Ang-(1-7) levels were found to be reduced in a small cohort of COVID-19 patients [ 270 ], administration of soluble recombinant human ACE2 proteins may be beneficial as a novel biological therapeutic to limit or even combat the progression of an infection caused by coronaviruses that utilize ACE2 as a receptor.…”

ACE2: The Major Cell Entry Receptor for SARS-CoV-2

“…Soluble hrACE2 (shrACE2) retains attractive physiological features due to its ability to inactivate SARS-CoV-2 present in the extracellular milieu. Differently from antiviral or anti-inflammatory therapies, shrACE2 can act upstream by decreasing the binding between SARS-CoV-2/mACE2, thus reducing infectivity [80]. Furthermore, it can also counteract the increase in AngII and DEABK/LDEABK preserving lung function.…”