Soluble ACE2 as a potential therapy for COVID-19

Abstract

Soluble angiotensin converting enzyme 2 (sACE2) could be a therapeutic option to treat coronavirus disease 2019 (COVID-19) infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) utilizes ACE2 receptors on cell surfaces to gain intracellular entry making them an ideal target for therapy. High-affinity variants of sACE2, engineered using high-throughput mutagenesis, are capable of neutralizing COVID-19 infection as decoy receptors. These variants compete with native ACE2 present on cells by binding with spike (S) protein of SARS-CoV2, making native ACE2 on cell surfaces available to convert angiotensin-II to angiotensin-1,7, thus alleviating the exaggerated inflammatory response associated with COVID-19 infection. This article explores the use of sACE2 as potential therapy for COVID-19 infection.

The pivotal link between ACE2 deficiency and SARS-CoV-2 infection: One year later

“…Indeed, high-affinity variants of soluble ACE2 bind to spike protein of SARS-CoV-2 and thereby neutralize infection as decoy receptors. These high-affinity variants outcompete native ACE2 present on cells by binding with the S protein of SARS-CoV-2, making native ACE2 on cell surfaces readily available for conversion of Ang II to Ang 1,7 [63] .

Figure 3 Potential therapeutic approaches of restoring the ACE2/Ang1-7 pathway or to trap the virus and to stimulate the renin-angiotensin-aldosterone system protective pathway.

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Developing Cytokine Storm-Sensitive Therapeutic Strategy in COVID-19 Using 8P9R Chimeric Peptide and Soluble ACE2

“…The concentration of inflammatory cytokines also dropped dramatically. According to the results of this report, it seems that hrsACE2 can have protective enzymatic effects in COVID-19 patients (Zoufaly et al, 2020;Krishnamurthy et al, 2021). So, sACE2 may contribute to make a balance between Ang-II and Ang-(1-7) and also prevent inflammation caused by the virus.…”

Soluble Angiotensin Converting Enzyme 2 (ACE2) Is Upregulated and Soluble Endothelial Nitric Oxide Synthase (eNOS) Is Downregulated in COVID-19-induced Acute Respiratory Distress Syndrome (ARDS)

“…Indeed, human recombinant sACE2 molecules have been shown to be effective in neutralizing COVID-19 infection by acting as decoy receptors [ 23 ]. These recombinant molecules can compete with ACE2 on endothelial cell surfaces for binding to SARS-CoV-2, leaving the membrane-bound ACE2 unoccupied and able to convert angiotensin II to angiotensin (1–7), thus moderating the overwhelming inflammatory response seen in COVID-19 [ 32 ]. A dramatic rise in sACE2 in one critically ill COVID-19 patient with ARDS, which preceded the recovery of the patient, prompted the authors to suggest that sACE2 represents an endogenous non-specific protective mechanism against SARS-CoV-2 infection [ 33 ].…”