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World.- Angiotensin-(1-7) is a key peptide in functions such as blood pressure regulation and inflammatory response, but is generated less when coronavirus enters cells. Pharmacologists from the Autonomous University of Madrid and the University of Manchester propose to use compounds similar to this to reduce the serious lung damage associated with COVID-19.
A European team of researchers proposes that angiotensin-(1-7)-analog drug therapies could be effective in reducing serious lung complications associated with SARS-CoV-2 infection, the coronavirus causing COVID-19 disease now converted into a pandemic.
The work, published in the journal Circulation, is signed by Concepción Peiró, from the Department of Pharmacology of the Faculty of Medicine of the Autonomous University of Madrid (UAM), and Salvador Moncada, of the Cancer Research Centre of the University of Manchester (United Kingdom).
It is proposed to use analogues of angiotensin-(1-7), a peptide that helps regulate blood pressure and the inflammatory response that is reduced when the virus enters the cell
Angiotensin-(1-7) is an essential peptide to help regulate blood pressure and inflammatory response. However, its presence is reduced when the coronavirus enters the cell due to a number of related processes.
The pathogen needs to bind to the proteins of human cells in order to enter and replicate within it, thus undertaking new cycles of infection towards other cells.
SARS-CoV-2 is coupled in the cell membrane to the protein ECA2 (angiotensin-2 converting enzyme), which is found in numerous tissues, especially in some such as the pulmonary epithelium and the endothelium of blood vessels. This is probably due to the marked lung damage associated with coronavirus infection.
But this ECA2 protein also plays a very important role in an organic peptide system called the renin-angiotensin (SRA) system, which is critical for the regulation of blood pressure, electrolyte balance, inflammatory response and other tissue maintenance functions.
Angiotensin II versus angiotensin-(1-7)
The main effector or substance that drives THE SRA is angiotensin II, a peptide that once its function has fulfilled (e.g. vasoconstrictor) must be degraded through the protein ECA2 into another that is considered its natural antagonist, angiotensin-(1-7), which exerts anti-inflammatory, vasodilator and antioxidant actions, among others.
When the virus binds to the ECA2 protein, it does not perform well, it accumulates more angiotensin II and less angiotensin-(1-7), which worsens inflammation and lung damage
The problem is that when the virus binds to the ECA2 protein, it disappears from the membrane of the cells and stops exercising its function correctly, which implies that more angiotensin II accumulates and less protective angiotensin-(1-7) is generated.
“In the serious lung complications that may occur as a result of infection, this deficiency would only worsen inflammation and lung damage,” says Concepción Peiró.
“Therefore,” he concludes, “, to reduce the serious lung damage associated with SARS-CoV2 infection, angiotensin analogues-(1-7), which are still being validated in clinical trials, or other drugs already used in clinical practice whose action is to limit the excessive effect of angiotensin II by blocking receptors mediating their actions.”
Source: Circulation
