How exactly does COVID-19 coronavirus infect human cells? What are the implications for the treatment of hypertension by ACE inhibitors and angiotensin receptor blockers?
Transcript of video
Professor Farzan, you discovered the receptor for SARS coronavirus in 2003. COVID-19 Coronavirus is about 80% similar in sequence to the SARS virus. How exactly does COVID-19 coronavirus infect human cells? How can this knowledge be exploited? Because of its similarity to SARS coronavirus. We tend to call SARS one now. SARS-CoV-2 uses the same receptor. It uses cell entry mechanisms that are very similar to what SARS one uses to infect cells. Specifically, it latches on to a receptor called ACE2. And then, by recognizing that receptor, it undergoes a series of changes that allow for the viral genetic material to get into the cell. Are there any implications for the treatment of hypertension by ACE inhibitors and angiotensin receptor blockers? First, let’s do some simple things. There are two classes of renin-angiotensin inhibitors. Those that target a receptor called an ACE1. This is a standard target for high blood pressure medications. ACE Inhibitors and Angiotensin receptor blockers do not work against ACE2. ACE2 receptor is a receptor for the SARS-1 virus and the COVID-19 virus. Although ACE inhibitors (medications to treat blood pressure) modulate the renin-angiotensin system and can change the efficiency of expression of both ACE1 and ACE2, they don’t directly impact the ability of the COVID-19 virus to get into the cells. Similarly, the ACE2 receptor has itself an enzyme site that can be targeted. But again, targeting that site has no direct impact on the ability of the virus to get into cells. However, as I sort of alluded to, the ability to manage high blood pressure and your angiotensin levels can impact the expression level of ACE2 on critical cells. And that ability to modulate is quite complex and affected by a number of things, including smoking, hypertension, and drugs that treat hypertension. And because the relationships are complex, I think it is, at this moment, unclear whether the drugs that treat hypertension impact the efficiency with which the virus replicates. The consensus of this moment is that it is better to control one’s blood pressure. It’s best to perhaps limit the expression of an ACE2 receptor, rather than to do any changes to one’s hypertension current treatment at the moment. But I have to say research is still very much ongoing. And it will be critical to follow that in the coming months. The frequency of suboptimally treated hypertension or untreated hypertension is also very high. So do you think that any conclusions can be drawn that people with hypertension are more susceptible to being infected? Or is it just a statistical aberration, because both hypertension and other heart diseases are just so prevalent. Hypertension is probably a risk factor. The only real question is whether once you have to continue to control that hypertension. I think the answer at this point is yes. But hypertension does appear to increase the amount of ACE2 receptor on critical cells. Does increased COVID-19 risk include also treated hypertension? In other words, if somebody has hypertension well under control, is there still an upregulation of the ACE2 receptor irrespective of treatment? Or does that only refer to untreated hypertension? COVID-19 risk is related to untreated hypertension at this moment. There is still ongoing research. It is not yet clear whether treated hypertension is a risk factor. But the consensus at this moment is to continue to treat hypertension. So do not change your hypertension treatment drug regimen at this point.