Quote:
Originally Posted by O.city
|
Okay, buckle up, cause this is going to be a long, somewhat speculative ride:
The main regulatory pathway in our body that controls BP is called RAAS (renin angiotensin aldosterone system). Renin is secreted by the kidneys and it converts angiotensinogen to angiotensin. Angiotensin is coverted by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases vasopressin production, vasoconstriction of arterial and venuous smooth muscle, and aldosterone secretion. All of these lead to an increase in BP.
Now, as a positive feedback loop would lead to runaway BP escalation and stroke, MI, or hemorrhage, it is necessary that our bodies have regulatory systems to counteract these changes. One of those enzymes is ACEII. It converts angiotensin II into angiotensin 1-7 and 1-9, both of which have cardioprotective and BP lowering effects and (IIRC) a reduction in inflammatory processes.
While I know that this drug is designed to modulate the ACE2 system, I haven't come across information stating exactly how it does it. I would assume that it operates as a partial/full agonist of ACE2. If that is the case, then you could in effect occupy those receptors, but only if it exhibits competitive agonism with some degree of being irreversible.
The benefits would be this: imagine the cell receptor like a USB port. In this case, the USB port is the ACE2 receptor. APN01 fits in and it has a copy of Malware Bytes installed. The virus also fits, but it's loaded with malware. If you occupy all of the USB ports with the APN01, the virus would have nowhere to go (assuming it only has one attachment site). If you occupy enough of the ports, the virus may not have enough to establish a foothold. If you occupy some of the ports and the cellular pathway initiated by the agonism of ACE2 results in anti-inflammatory processes being ramped up, you can mitigate the deleterious effects of the virus (ARDS, etc.).
At this point, I know very little about the drug, but I would have a few questions:
1) What is your delivery system? You can't give proteins orally in almost all cases due to massive degradation in the GI tract due to pH and proteases.
2) How scalable is this? Could this be done with nanoparticles (lipid, gold, liposomes)? Biologics are extremely difficult to produce in large quantity.
3) What is its prior efficacy? It looks like it has been previously used for pulmonary arterial hypertension. I'm not sure where it stalled exactly (Phase III, perhaps?), but if it's not activating ACE2 enough to exhibit BP lowering effects, is it going to be able to do enough to mitigate SARS-CoV-2 entry or reduce the inflammatory processes? Maybe we're lucky and it's like Viagra, another failed BP med whose MOA led to other positive effects.
It's an interesting concept, but much is unknown.