Ivermectin and COVID-19

This topic has perhaps already been discussed, but I did not see it upon a quick glance. Here were eight points given as to how Ivermectin can be used as an effective treatment for COVID-19:

The mechanism that I am interested in is that Ivermectin acts as a protease inhibitor that is effective at reducing the ability of the SARS-CoV-2 virus to replicate. Based on this mechanism, as well as the eight points above, is there specific information refuting that Ivermectin reduces the ability of the SARS-CoV-2 virus to reproduce itself as described?

Well, drinking bleach in sufficient quantities also reduces the ability of the  SARS-CoV-2 virus to reproduce itself.  Not much of a claim.

The more critical question is whether Ivermectin is more effective at preventing COVID than an FDA approved vaccine.  The answer from the CDC seems to be a resounding no. 

Drinking bleach has side effects that Ivermectin doesn't. Comments like these are unhelpful. You also didn't answer the question because I'm not asking about the vaccine. I'm honestly asking about Ivermectin as a protease inhibitor. Do you have specific information about that?

the consensus within science is that ivermectin is unsafe. also, you would have to cite credible authority to back up all your claims, cause there's so much misinformation floating around that dupes stupid people, that we can't just assume information we find on the internet is true. 

Ivermectin, an inexpensive drug used to kill parasites, has been falsely touted as a treatment for COVID-19. The FDA and medical experts warn against the use of ivermectin to treat the disease. Large studies testing the drug against COVID-19 are ongoing.
Social media users have coined the term “Pfizermectin” in their posts claiming that ivermectin and Pfizer’s new oral antiviral, PF-07321332, are the same drug. According to Pfizer, the drug is being tested in combination with the HIV drug ritonavir in a study on 2,660 people.
There is no relationship at all between the two drugs, said Dr. William A Petri, professor of infectious diseases at the University of Virginia.
“The only way they are alike is that they are both pills,” Petri said.
Dr. Kevin J. Downes, assistant professor of pediatrics at the Perelman School of Medicine of the University of Pennsylvania, agreed, “They are dramatically different molecules. The drugs are different in their structure and their molecular size.”
The drug being studied by Pfizer acts as a protease inhibitor, which prevents a virus from replicating. Other protease inhibitor drugs helped revolutionize the treatment of HIV.
Several posts circulating online wrongly suggest that the pills are the same because ivermectin also acts like a protease inhibitor and keeps the virus from replicating. Ivermectin continues to be studied in relation to COVID-19, however, it has yet to be proven that it can treat COVID-19.
Images of the structure of Pfizer’s new pill and ivermectin can be found online and do not show similarities like the posts describe.
Ivermectin binds to glutamate-gated chloride channels and is used to treat parasite infections, said Joseph Glajch, a consultant in pharmaceutical and analytical chemistry.
“These two are so far apart,” he said. “If you look at how they interact with the body..., they don’t even go to the same pathways or receptors.”

Are these effects verified at a particular human dosage? Or do they come from in-vitro, (or in-silico) studies where ivermectin is introduced to a COVID infected cell culture?

What often happens is that a particular drug has an impact on cells in-vitro, in a way that is not replicable through possible medication.

A great example is of the famous headline “sniffing farts cures cancer”.

What makes you say that?

well, it has risky side effects. i suppose that's all i can say for sure. that, and that animal doses are for sure unsafe. 

I like your funny words magic man. Without even a single source, I could claim that TNT can prevent the virus from harming the person because the person is already dead. What is the point? 

The side effects seem fairly mild. And they often occur because of the body's reaction to the dying parasites that Ivermectin is used for.

I do agree that there is misinformation from both sides. What I want to know though is why the media is demonizing a relatively safe drug that is routinely administered to humans around the world by calling it "horse paste" and making it seem super dangerous to ever use. It seems intentionally misleading. That's why I'm looking for specific information regarding the nature of Ivermectin as a protease inhibitor.

Popular drug where I am. 

In silico = computer simulation

Right, but it's based on other data. I would think that by now, we would have some idea of what Ivermectin does when it is taken. What I'm essentially asking is if we have verified that Ivermectin acts as a protease inhibitor. And if so, does it do so in the specific way as claimed in my OP? If there is evidence against it acting as a protease inhibitor, I am interested to hear that too.

So I think it’s quite possible that it could be an inhibitor - but not in a way conductive to be a therapeutic.

To start, I think it's important to recognize that ivermectin is, at least, an improvement upon HCQ, which had a much less favorable toxicity profile.

That being said, many of the same problems with HCQ exist with ivermectin. Both drugs have effects on viral replicases at high enough concentrations, though it's notable that the concentration achievable without yielding toxic effects in vivo is far lower than the established dose required to inhibit these replicases in vitro. 

"An important controversial point to consider in any rationale is the 5 µM required concentration to reach the anti-SARS-CoV-2 action of ivermectin observed in vitro,17 which is much higher than 0.28 µM, the maximum reported plasma concentration achieved in vivo with a dose of approximately 1700 µg/kg (about nine times the FDA-approved dosification)."

The above article details several problems with the proposed mechanisms and implementation of ivermectin, though this one seems the most daunting. In fact, this is a problem regardless of the mechanism: any actual effectiveness must be established at concentrations that are achievable without substantial side effects in vivo. HCQ couldn't achieve it, and ivermectin looks to be in the same boat. 

As for addressing the other specific mechanisms you've provided, those would take quite a bit more research, but concentration-dependence is at least a point of substantial concern. The in silico analyses of what the drug could do give some good reason to believe it could be effective (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996102/), but they're purely theoretical. Even when taking more direct studies into account (this is still in vitro), these suggest a very specific interaction between ivermectin and 3CLpro (the protease used by the virus) that would likely to be overcome by mutation if this intervention was employed widely enough (https://www.nature.com/articles/s42003-020-01577-x). I will note that its antiviral activity, like antibiotics used against bacteria, can easily drive viral evolution, likely without sacrificing virulence.

If you look at this site: https://www.cell.com/trends/parasitology/fulltext/S1471-4922(20)30290-7

It says that for Ivermectin you need a dose of 350 ng/ml for deworming and you need 4375 ng/ml for SARS-Covid-2 inhibition.

It also state that large doses can cause brain damage.

The concentration issue seems to be an important one to be addressed. That's helpful to know.

I shouldn't have included the whole list since I was specifically considering it as a protease inhibitor. I think I have understood the points you made, which have been helpful in understanding this claim in better detail. It can be tedious sifting through all the information to get straight answers to some of these questions, thanks.

People will try any old shit when they are desperate.

I tend to go for the stay away from crowds of idiots,  and a mask approach.

Oh and a specific Covid Vax  x2...... Soon to be x3. (Perhaps a benefit of living where I do...Though some Conspiracy Theorists will surely disagree).

And if I ever get worms I'll perhaps give Ivermectin a go.

(Conspiracy Theorists....Covid Vax bad....Ivermectin good...There's logic for you).

Though I tend to steer clear of parasite infested food. (Perhaps also, a benefit of living where I do).

Good for you. If there's a benefit like that, you should always use it.