scholarly journals A Dual-Route Perspective of SARS-CoV-2 Infection: Lung- vs. Gut-specific Effects of ACE-2 Deficiency

2021 ◽  
Vol 12 ◽  
Author(s):  
Elizabeth M. Sajdel-Sulkowska

SARS-CoV-2, primarily considered a respiratory virus, is increasingly recognized as having gastrointestinal aspects based on its presence in the gastrointestinal (GI) tract and feces. SARS-CoV-2 uses as a receptor angiotensin-converting enzyme 2 (ACE-2), a critical member of the renin-angiotensin-aldosterone system (RAAS) involved in the regulation of blood pressure and fluid system. In addition to the systemic endocrine functions, RAAS components are also involved in intracrine and organ-specific local functions. The angiotensin-converting enzyme 2 (ACE-2) is a key component of RAAS and a receptor for SARS-CoV-2. It is expressed in many tissues with gastrointestinal (GI) tract ACE-2 levels far exceeding those in the respiratory tract. SARS-CoV-2 binding to its receptor results in a deficiency of ACE-2 activity in endocrine, intracrine, and local lung and GI tract ACE-2. The local ACE-2 has different organ-specific functions, including hypertension-independent activities; dysregulations of these functions may contribute to multiorgan COVID-19 pathology, its severity, long-term effects, and mortality. We review supporting evidence from this standpoint. Notably, COVID-19 comorbidities involving hypertension, obesity, heart disease, kidney disease, and diabetes are associated with gastrointestinal problems and display ACE-2 deficits. While RAAS inhibitors target both endocrine and intracrine ACE-2 activity, the deficit of the local ACE-2 activity in the lungs and more so in the gut have not been targeted. Consequently, the therapeutic approach to COVID-19 should be carefully reconsidered. Ongoing clinical trials testing oral probiotic bound ACE-2 delivery are promising.

Author(s):  
Sho Mokuda ◽  
Tadahiro Tokunaga ◽  
Junya Masumoto ◽  
Eiji Sugiyama

AbstractDetected in December 2019, the coronavirus disease 2019 (COVID-19) has since spread all over the world, resulting in a global pandemic. The disease is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), and its symptoms usually include cough, fever, and gastrointestinal problems. Although the prevalence of rheumatoid arthritis (RA) is about 1 % of the global population and RA patients naturally have a chance of acquiring COVID-19 in this pandemic, no studies have considered the expression of angiotensin-converting enzyme 2 (ACE2) (a receptor for SARS-CoV-2) in synovial tissues. Our presenting data revealed that ACE2 expression was elevated in active rheumatoid synovium, and siRNA against STAT3 was able to downregulate ACE2 expression, which was in turn induced by IL-6 signaling.


2020 ◽  
Vol 22 (12) ◽  
pp. 31-36
Author(s):  
Marina V. Leonova ◽  

COVID-19 pandemic is currently the most pressing public health problem worldwide. Despite growing knowledge about the nature of SARS-CoV-2-assosiated severe acute respiratory syndrome, the treatment options are still poorly defined. The safety of nonsteroidal anti-inflammatory drugs (NSAIDs), in particular ibuprofen, has been questioned without any supporting evidence. This has contributed to a number of observational studies evaluating the effect of ibuprofen on COVID-19 disease outcomes. A search of publications was carried out and a systematic review of 9 studies was presented, pharmacodynamic effects of ibuprofen were considered in terms of the effect on angiotensin-converting enzyme 2 and cyclooxygenase. The studies data have shown no direct interaction between ibuprofen and SARS-CoV-2, no evidence that ibuprofen affects the up-regulation of angiotensin-converting enzyme 2 as a COVID-19 receptor in human studies. Observational studies have not found evidence that ibuprofen, when used chronically before COVID-19 or when acutely used to relieve symp-toms of COVID-19, contributes to infection or increases the risk of adverse outcomes (mortality, risk of hospitalization, risk of mechanical ventilation). Subse-quently, international regulatory authorities (World Health Organization, European Medical Agency, FDA) concluded that there is no link between the more severe course of COVID-19 and NSAID treatment; paracetamol and other NSAIDs (ibuprofen) are recommended to treat the symptoms of COVID-19; patients on chronic NSAID treatment are warned not to discontinue it, as their condition may worsen.


2020 ◽  
Author(s):  
Cristina Garcia-Iriepa ◽  
Cecilia Hognon ◽  
Antonio Francés-Monerris ◽  
Isabel Iriepa ◽  
Tom Miclot ◽  
...  

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>


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