All publications of IN-28190 . Dehra Dun , India
ACEi/ARB and COVID-19
Pharm-D (II P.B), PES College of Pharmacy, Hanumanthnagar, Bangalore, Karnataka, India
The etiological basis of corona virus disease 2019(COVID-19) pandemic infection is SARS-COV-2 i.e. severe acute respiratory syndrome corona virus-2. Many viruses has been found that produces cellular receptor modulation, which includes HIV, influenza C virus, measles virus, herpes virus and so do corona virus have similar property.
Two integral proteases angiotensin converting enzyme 2 (ACE2) and Neutral amino-peptidase N (APN) of Renin Angiotensin System (RAS), which has its vital role in physiology of cardiovascular system (CVS), promotes the facilitation of cellular entry of SARS-COV-2.
Renin expression over the alveolar mast cells, that inhabits the upper and lower respiratory tract, elicit pulmonary angiotensin II (AngII) and during infection of SARS-COV-2, this pulmonary RAS has negative impact.
Even for HCOV-NL63, the primary entry receptor is ACE2.
Pathophysiology of corona virus is the highly complex process.1
After going through the above information, the students and interns in the medicine profession, the first thing that strikes the mind is, Why then angiotensin receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACEi) are not used as an intervention to treat COVID-19?
But, the selective blockade of synthesis of AngII or induced activity leads to increase in the expression of ACE2 gene and hence activity of ACE2
Moreover, ACE2 is unsusceptible to ACEi.3, 4
ACE (angiotensin converting enzyme) has a single HCZZX Zinc binding site which is similar to one of the active domain of ACE2, and overall 40% identical to ACE.4
If that 60% difference between the two is monitored closely at molecular and genetic level, then there can positive hope for new drug development to fight COVID-19 and not only SARS-CoV-2 but also other virus that makes there lifecycle possible in the human body using ACE2.
In recent reports from China and Italy have pointed out that many people those who died in pandemic because of COVID-19 were having the medical history of hypertension and were on the ARB/ACEi.
Recently on March 30, 2020, the interventional clinical trial has been started, in which only those subjects will be enrolled who are already taking ACEi/ARB.
All the subjects will be randomly divided into two groups in which, for group 1 there will be switch to alternative blood pressure medications form ARB/ACEi and group 2 will continue to remain on ARB/ACEi, to identify that whether the risk of COVID-19 increase with commonly prescribed drugs or not.2
Study title: CORONAvirus Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptor Blockers InvestigatiON: A Randomized Clinical Trial
Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 2414 participants
Masking: None (Open Label)
Actual Study Start Date: March 30, 2020
Estimated Primary Completion Date: January 31, 2021
Estimated Study Completion Date: March 1, 20212
The Results are awaited.
1. Wevers B.A. ”Renin Angiotensin System in human corona virus pathogenesis”, Future Virology, volume 5 No. 2, Future medicine, March 1, 2010
2. McEvoy J.W. “coronavirus ACEi/ARB investigation (CORONACION)” clinicaltrial.gov, U.S. National Library of Medicine, April 1 2020
3. Ferrario C.M. et.al “Effect of angiotensin receptor blockers and angiotensin converting enzyme on cardiac Angiotensin Converting Enzyme 2”, AHA, Circulation, volume111 No. 20, May 16, 2005, page no. 2605-2610
4. Zisman L.S. “ACE and ACE2: A tale of two enzymes”, European Heart Journal, volume 26, issue 4, February 2 2005, page no. 322-324.