How the coronavirus infects human cells
By: David Seaman
The novel coronavirus that emerged in late 2019 called SARS-CoV-2 enters cells by binding to an enzyme called angiotensin converting enzyme-2 (ACE2). I have noticed that this enzyme is referred to by many as the ACE2 receptor. You should understand that ACE2 is NOT a receptor, it is an enzyme. The primary function of ACE2 is to convert a pro-inflammatory substance called angiotensin II into anti-inflammatory angiotensin-(1-7). ACE2 was discovered around the year 2000, which is why it is not a well-known enzyme (1).
Angiotensin II increases blood pressure and also promotes inflammation and lung damage, which is counteracted by angiotensin-(1-7), which means we need to produce an adequate amount of angiotensin-(1-7) to balance the effects of angiotensin II. This does occur in healthy people, in which a balance is struck between angiotensin II and angiotensin-(1-7) by the actions of ACE2. Unfortunately, variable degrees of ACE2 deficiency are found in the elderly population, as well as in people with diabetes, hypertension, and heart disease. These are the same people at a greater
risk for a poor outcome if infected by SARS-CoV-2 (2).
It should be understood that diabetes, hypertension and heart disease almost always share a common problem, that being elevated blood glucose levels. The metabolic syndrome is a hyperglycemic state (high blood glucose levels), which leads to the development of diabetes, hypertension, heart disease, and most other chronic diseases. Too much glucose in circulation leads to a process called glycosylation, wherein proteins become
“sugar coated.” You may have heard of hemoglobin A1c, which is also referred to as glycosylated hemoglobin. Practically speaking this means that hemoglobin in red blood cells gets “sugarcoated.” Hemoglobin A1c is the most commonly measure glycosylated protein. It turns out that
ACE2 can also become glycosylated, which appears to increase the ability of SARS-CoV-2 to infect lung cells (3).
Once a lung cell is infected by SARS-CoV-2, there is a further reduction of ACE2 activity, which further magnifies the imbalance between lung damaging angiotensin II and lung protective angiotensin-(1-7). This helps to explain why people with hyperglycemia (diabetes, hypertension,
and heart disease) are at a greater risk for developing a severe case of COVID-19 (1,2). The coronavirus more easily gains access to lung cells due to the glycosylation of ACE2, and once infected there is a greater reduction in ACE2 activity, which enhances the pro-inflammatory imbalance between angiotensin II and angiotensin-(1-7). I created a video to illustrate how this
process works (4).
Vitamin D also has an effect on ACE2. It turns out that vitamin D enhances the expression of ACE2 (5). This means that vitamin D exerts many effects that are beneficial against viral infections, including inflammation reduction and the production of anti-microbial peptides
(cathelicidins and defensins) (5).
- Donoghue M, Hsieh F, Baronas E, et al. A novel angiotensin-converting enzyme-related
carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000;87:E1–E9.
- Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency
and SARS-CoV-2 infection. Eur J Intern Med. 2020; April 20. [Epub ahead of print]
- Ceriello A. Hyperglycemia and the worse prognosis of COVID-19. Why a fast blood glucose
control should be mandatory. Diabetes Res Clin Pract. 2020;163. Available online April 29, 2020.
- ACE2 receptor: how the coronavirus enters human cells. DeFlame Nutrition YouTube channel.
- Gombart AF. The vitamin D-antimicrobial peptide pathway and its role in protection against
infection. Future Microbiol. 2009;4:1151.
Dr. Seaman has been writing about chronic inflammation for almost 30 years. He wrote the first published scientific article about how diet can induce inflammation and promote pain. His articles about pain, inflammation, diet, and obesity have been referenced by researchers at the Centers for Disease Control (CDC), Harvard Medical School and many other universities in the United States, as well as universities in Canada, Brazil, Europe, Middle East, India, Australia, Russia, and other
Asian countries. He can be found at www.DeFlame.com and www.drdavidseaman.com.
Dr. Gibson was fortunate enough to have Dr. Seaman as a professor while attending Palmer Chiropractic Florida from 2007-2010. Dr. Gibson has the Deflame Diet book on sale at his office. Please call today to learn more.