Manipulation of ACE2 expression in COVID-19

Abstract

SARS-CoV-2 is the virus responsible for the ongoing COVID-19 outbreak. The virus uses ACE2 receptor for viral entry. ACE2 is part of the counter-regulatory renin-angiotensin-aldosterone system and is also expressed in the lower respiratory tract along the alveolar epithelium. There is, however, significant controversy regarding the role of ACE2 expression in COVID-19 pathogenesis. Some have argued that decreasing ACE2 expression would result in decreased susceptibility to the virus by decreasing available binding sites for SARS-CoV-2 and restricting viral entry into the cells. Others have argued that, like the pathogenesis of other viral pneumonias, including those stemming from previous severe acute respiratory syndrome (SARS) viruses, once SARS-CoV-2 binds to ACE2, it downregulates ACE2 expression. Lack of the favourable effects of ACE2 might exaggerate lung injury by a variety of mechanisms. In order to help address this controversy, we conducted a literature search and review of relevant preclinical and clinical publications pertaining to SARS-CoV-2, COVID-19, ACE2, viral pneumonia, SARS, acute respiratory distress syndrome and lung injury. Our review suggests, although controversial, that patients at increased susceptibility to COVID-19 complications may have reduced baseline ACE2, and by modulating ACE2 expression one can possibly improve COVID-19 outcomes. Herein, we elucidate why and how this potential mechanism might work.

Factors regulating dynamics of angiotensin-converting enzyme-2 (ACE2), the gateway of SARS-CoV-2: Epigenetic modifications and therapeutic interventions by epidrugs

“…The tissue-specific expression of ACE2 enhances the vulnerability of specific organs for SARS-CoV-2 infection. For example, heightened expression of ACE2 protein in the lungs and heart increased their vulnerability for SARS-CoV-2 infection [37] . Apart from those various other parameters are taken into consideration while discussing the viral entry into the host cells [38] .…”

Anti-TNF-α agents Modulate SARS-CoV-2 Receptors and Increase the Risk of Infection Through Notch-1 Signaling

“…Circulating ACE2 (plasma ACE2) is produced after being shed from cell membranes due to membrane protease effects ( 31 ). A high level of circulating ACE2 has been associated with a better outcome in patients with influenza A H7N9 infection ( 32 ).…”

Probiotic consortia improve anti-viral immunity to SARS-CoV-2 in Ferrets

“…This hypothesis is supported by increased IFNA expression by OL-1 and OL-2 compared to placebo at D5 ( Figure 2 ) and suggests activation of the type I IFN pathway in the gut. On the other hand, ACE2 also acts as the SARS-CoV-2 receptor, and further, higher ACE2 expression has cytoprotective effects (Gheblawi et al, 2020), and thus it is not clear what is an optimal level of ACE2 expression (Chaudhry et al, 2020). Despite increase in ACE2, we did not observe differences in the duodenal tissue inflammation ( Figure 2 ) or in inflammatory gene expression response between the treatments at D5 ( Figure 3 ).…”