SARS CoV 2 continues to wreak havoc by causing various complications including respiratory distress, pneumonia, and death in extremely severe cases. Attachment of the virus to the host cell receptor is obligatory for it to produce more copies of itself and induce pathogenesis. SARS CoV 2, like any other virus, does not have a metabolism of its own. That is the reason for its dependence on the host cell.
An enzyme called angiotensin converting enzyme 2 (ACE2) acts as a port of entry for the dreadful SARS CoV 2. The spike protein, which gives a crown-like appearance to the virus binds to this ACE2 receptor on the host cell. Nevertheless, ACE2 as such is beneficial to the body.
ACE2 participates in a mechanism called the “renin angiotensin system”. This is a feedback mechanism and commences whenever the blood pressure becomes low. Precisely said, the renin angiotensin system compensates for this reduction in blood pressure.
The kidney initiates the mechanism by secreting an enzyme, renin and the process continues. At one particular point, there is a synthesis of a hormone angiotensin 2, which constricts the blood vessels and elevates the blood pressure.
To balance this high blood pressure, ACE2 (SARS CoV 2 receptor) converts the angiotensin 2 into angiotensin 1-7 whose functions are antagonistic to that of angiotensin 2. In other words, angiotensin 1-7 dilates the blood vessels and ultimately reduces blood pressure. Thus, ACE2 stabilizes blood pressure and carries out a protective role in the body. Considering this, in hypertensive patients, medications are aimed at upregulating the expression of ACE 2.
A hypothesis existed that these antihypertensive drugs aggravate the severity of COVID-19. However, it has not been established so far. As pointed out by the European Society of Cardiology, there is no strong scientific evidence to support this notion against the usage of antihypertensive drugs in COVID-19 patients.
In fact, experimental animal studies reveal that these drugs could be protective against serious lung complications. So, it is too early to arrive at firm conclusions and extensive studies would pave the way to clarity.
Speculations are revolving around COVID-19 and cigarette smoking. Two different opinions prevail. Some argue that smokers are at reduced risk for COVID-19. On the contrary, some studies have conveyed the opposite. Recently, a planned controlled study demonstrated that smoking increases the expression of ACE2 receptors on the lung cells. Furthermore, people who had refrained from smoking for a minimum of 12 months had a 40% reduction in their ACE 2 expression levels.
Continuous smoking leads to the expansion of lung cells to produce more mucus. The secreted mucus forms a protective layer on the respiratory tract. However, besides mucus secretion, this cell expansion might also increase the secretion and expression of ACE2 receptors. This elevated ACE2 expression level in turn facilitates more virus particles to bind to the cell.
This said, COVID-19 cannot be projected as a disease that affects the respiratory tract alone. For instance, ACE2 receptors are expressed at a considerable level in the intestine. Some COVID-19 patients manifested vomiting and diarrhea. Examination of their stool specimens revealed the presence of SARS CoV 2. This has raised concern for potential faeco-oral transmission of COVID-19.
Liver enzymes such as aminotransferase were also substantially increased suggesting a direct injury to the liver, thanks to the attachment of SARS CoV-2 to the ACE2 receptors in the liver cells. However, these enzymes are non-specific biomarkers, given their elevation in most viral diseases. This makes it difficult to draw conclusions based on this finding alone.
The extent of the dissemination of ACE2 in the body largely determines the pathogenesis of COVID-19. However, considering the beneficial role played by the enzyme in the body, it is not rational to develop treatment protocols that directly inhibit their expression levels. Rather, inhibiting the interaction between ACE2 receptor and SARS CoV 2 would be a promising drug target.
In view of this, a human recombinant soluble ACE2 drug has been subjected to trials. This drug does not attach itself to the host cells. Instead, it acts as a decoy receptor and binds to the invading SARS CoV 2. This prevents the virus from binding to the natural host cell ACE2 receptor. Further investigation might elucidate the effectiveness of drugs targeting ACE2.
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