Paxlovid is not the same as ivermectin
How Pfizer’s new drug stops covid
On November 5th, Pfizer announced results for their new drug, Paxlovid. In their study, none of the 600 patients treated with the drug died, while 10 died in the control group. Less than 1% of patients taking the drug ended up in the hospital, while 7% of the patients taking a placebo did.
For statistical reasons, we don’t know if the pill will always be 100% effective. Pfizer guesses it will cut the death rate by 90%.
This is great news. Previous covid treatments, like Remdesivir and Monoclonal antibodies, needed to be given via IV injection. Paxlovid is more effective and people can simply take it at home.
Between this and vaccines, it should be possible to stop most covid deaths. But it will take some time for Pfizer to ramp up production and the drug will have a high price tag, probably around $700. That’s more expensive than a vaccine but cheaper than Remdesivir and monoclonal antibodies. Both of those cost over a thousand dollars for the drugs, plus more for the doctors and nurses that give the injections. The Pfizer pill will be cheaper, more effective, and more convenient.
The response from conspiracy theorists has been predictable: they think Pfizer’s drug is repackaged ivermectin, a ploy to make money when we could all just take a cheap miracle drug instead.
Let’s look at how Pfizer’s drug works and how it differs from ivermectin.
When covid infects your cells, it first binds to ACE2 receptors on the cell surface. The virus’ membrane fuses with the cell membrane, and viral RNA leaks into the cell:
The viral RNA hijacks the cell’s machinery to make more viruses.
As a first step, a ribosome reads the RNA and turns it into a long protein.
Every 3 letters of RNA forms the code for one amino acid. Strings of amino acids fold up into proteins.
But the virus needs multiple proteins. It wants one for the spherical membrane, a different one for the spikes on the outside, and many other non-structural proteins.
An enzyme called 3CLPro chops up that long protein into pieces. Those pieces go on to become the parts of the new virus.
If you want to look a the life cycle in a bit more detail, the whole cycle looks something like this. 3CLPro is used at step number two:
There are many places you could stop a covid infection, so there’s more than one drug that could help. Some drugs might block covid from entering cells. Others might stop its replication inside of cells.
Paxlovid blocks the 3CLPro protease from chopping up the long protein into pieces. The virus can’t separate out which pieces to cut out and assemble. It can’t make copies of itself. Your covid infection quickly stops.
People across social media insist that Paxlovid is identical to Ivermectin. The most popular claim is this video from Dr John Campbell.
First off, Paxlovid is not the same molecule as Ivermectin:
Campbell claims that the two drugs still work the same way by referring to a paper called “Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents”.
In the video, he walks the viewer through the paper by underlining various words and phrases used:
Campbell reads that ivermectin also has some activity against 3CLPro. For some reason, he doesn’t underline the most important line in the paper, which is this:
The calculated IC50 values for ivermectin, tipranavir, boceprevir, micafungin, paritaprevir, and ombitasvir were found to be 21.5, 27.7, 31.4, 47.6, 73.4, and 75.5 µM, respectively.
IC50 is the dose required for the drug to work (that is, inhibit 3CLPro) 50% of the time. For ivermectin, you need 21.5 µM. If you go a bit above that, to 50 µM, it’s going to totally stop the virus. If you go below about 10 µM, it doesn’t do anything at all.
21.5 µM is a very high dose of ivermectin!
To show exactly how high this is, let’s do some math and calculate this in terms of tubes of horse paste.
One tube of horse paste is good for treating a 1250 pound horse at 200 µg/kg.
If a 180-pound person ate the whole tube, the dose would be 1400 µg/kg.
But 200 µg/kg is a normal human dose from taking one pill. That gets your blood concentration up to 0.057 μM.
If you take the pill with a meal, you might get up to 0.14 μM.
The drug concentrates in your lungs, getting up to 0.38 μM.
If you ate the whole tube, the concentration might get up to 2.7 μM.
That paper says you need concentrations of 21 μM.
To get ivermectin to work like the Pfizer pill, you would need to eat 8 tubes of horse paste.
So, the new drug is basically the same thing as ivermectin:
One other possible adjustment, ~90% of ivermectin binds to albumin in your blood, before it gets to the lungs, lowering the effective dose. So we might actually be talking 80 tubes. Either way, it’s not a safe dose.
And you would have to eat that dose every day until your covid is cured.
I do not recommend trying that. You would poison yourself. But, even, if that was safe, you’d find out that Pfizer’s drug is fairly priced.
A tube of horse paste costs $17 on Amazon. 8 tubes would be $136. That five-day horse paste binge will set you back $680.
Some people might be wondering… is there some smaller effect at a lower dose? Does ivermectin work half as well if you only take half as much?
Here’s a graph from the paper. There’s really no effect at all until about 10 μM (4 tubes of horse paste), and it doesn’t get strong until 20 μM:
It’s not enough to find a drug that shares the same mechanism as Paxlovid. You also need to find one that works in the right doses. That’s why we have big pharmaceutical companies to research this stuff.
If you screen a lot of drugs, it turns out that many can work in the same way. One paper suggests black tea could suppress 3CLpro, at some dose.
We should immediately know that tea doesn’t stop covid deaths. If it did, Britain would have easily fought off covid by drinking tea and John Campbell wouldn’t have a job making misleading Youtube videos.
There is something shady about the way Campbell presents information.
Every time he presents a paper, he insists you can look for yourself. 7 and a half minutes into the video, he says, “You can check it out for yourself here, I always paste the links, I don’t want you to believe what I say”.
I think this is a bit like a magician saying, “there’s nothing up my sleeve”.
It’s a bluff. You can go read the paper. You can find the IC50 of the ivermectin. You can read other papers to figure out what that number means, then do the math. Ivermectin won’t work the same way that Paxlovid does.
But that’s a lot of work. Doing math is harder than watching Youtube. So Campbell says: “I’ll read it for you. Leave it to me, I’ll tell you the truth.”
And then he lies to you.
Campbell underlines words in each paper, as if to show you he’s emphasizing the important parts. The repetition reminds me of ASMR videos. It’s like a technique to lull you to sleep.
When you first click on his video, you get an ad. What product did you see?
That company paid a few pennies, Youtube kept some of the money, Campbell got the rest. He has 1.3 million subscribers, so it adds up. He’s making a killing off of telling people what they want to hear.
He makes that money because people are too lazy to read scientific papers, they just want to sit back and feel like they’re being let in on secrets.
There’s a twist here. I didn’t prove that ivermectin can’t work. I only proved that it doesn’t work via that mechanism.
It’s hard to completely prove that a drug doesn’t work. If one experiment shows that a drug fails, it could still work at some different dose or in some combination of drugs.
The original paper that got people interested in Ivermectin showed you only need 2 μM to get an effect. That’s 10 times lower, still not a safe dose, but it’s closer to reality. It must be working on some mechanism other than 3CLPro.
That experiment was done in kidney cells, so we don’t know what happens in lung cells. An experiment done in May tried it out and found that ivermectin doesn’t work in lung cells. A new paper that came out in October 2021 suggested the drug does work in lung cells, with a low IC50 of only 0.2 μM.
So we have one experiment claiming that ivermectin can work at doses you could maybe reach with pills. We don’t know the mechanism it works on. It’s not 3CLPro, it might have something to do with a protein called importin alpha.
To actually know, we have to test it in patients. I don’t think that science is settled. It did not work in the largest randomized trial done in Brazil.
I’ve written about ivermectin before — there’s a lot of disinformation floating around. It’s not a miracle drug. It did not save India, or Mexico, or Peru. It’s not 100% effective against preventing covid. Dr Kory, the drug’s biggest promoter, actually got covid while he was taking ivermectin.
But it might still be possible it helps at large doses. At the moment, ivermectin supporters are pointing to a large trial in Argentina where large doses reduced hospitalizations by 50%. That wasn’t a randomized trial, so we’re not sure yet.
The trial in Argentina used a dose of 0.6 mg/kg, for 5 days, given with a meal. The Brazilian trial used only 0.4 mg/kg, for 3 days, given on an empty stomach. The open-minded thing to say is that ivermectin doesn’t work at the lower dose, but there’s still a chance it works at the higher dose.
The worst case for ivermectin is that it doesn’t work at all. The best case is that it works at high doses and we have a drug that’s cheaper than Paxlovid, but it only gives 50% protection instead of 90%.
Hopefully we’ll find out with better randomized controlled trials.
If it does work, we’ll have to do a cost/benefit analysis.
In Paxlovid’s trial, 7% of the placebo group ended up in the hospital, while only 1% of the trial group did. At $700 for the drug, it will cost $11,000 to keep one person out of the hospital.
That’s for “adults at high risk of covid”. If you gave the drug to everyone younger and healthier, it would cost even more. If you are healthy and under 65, I’m guessing you won’t be getting this pill any time soon.
It looks like you can get a 5-day course of ivermectin pills for about $100, in the United States. If it works, it would cost about $3,000 to keep one person out of the hospital. That’s about 4 times cheaper, but it wouldn’t save as many lives since it’s only 50% effective, not 90%. Anyone who could afford Paxlovid would choose it.
The US government paid $20 per dose of Pfizer vaccine. 2 shots cost $40. The vaccine was originally marketed as 95% effective, but it hasn’t worked out quite that well. Let’s say it’s 80% effective at keeping people out of the hospital. That costs $700 to keep one person out of the hospital.
The AstraZeneca vaccine is only $4 a dose. Two shots are $8. It’s not working quite as well as the mRNA vaccines. But, even if it’s 60% effective, that’s only $190 to keep one person out of the hospital.
Maybe $100 is too pricey for ivermectin and some countries could make it cheaper. It’s still going to be hard to beat $8. You would need to make both the pills and the covid tests cheaper than $8.
There isn’t a cheaper solution that we’re ignoring. People just want to sell you Youtube videos about that fantasy.
At the end of his video, John Campbell says that ivermectin is better than Paxlovid because it has multiple mechanisms of action.
He insists that Paxlovid will just cause covid to mutate such that the drug no longer works.
This is a very common argument used to trigger fear, uncertainty, and doubt.
We’ve seen this over and over through the pandemic. We’ve heard:
• “Lockdowns will kill more people than they save.”
• “Masks will suffocate people.”
• “Vaccines will kill more people than the virus.”
• “Vaccines will cause the virus to mutate.”
• “Merck’s drug is a global catastrophic threat.”
And now we have,
• “Pfizer’s drug won’t work, covid will just mutate.”
The reality is, covid will mutate no matter what. If we all get natural immunity, then the virus will slowly mutate to get around that. If we all get vaccinated, it’s the same. On Youtube, people freak out. In the real world we call this, “getting a new flu shot every year”.
Pfizer’s new drug should be hard for the virus to develop resistance to. Covid can avoid antibodies by changing its spike protein, but it's hard for it to change the 3CLPro enzyme. 3CLPro is the same across many coronaviruses, it doesn’t mutate much.
The reality about drug resistance is: we won’t know until we try it. The drugs we use to fight HIV are protease inhibitors. They’re still working, after a few decades. A drug called Amantadine was used to fight the flu. It took about 10 years before we started to see resistant strains and 35 years before we saw widespread resistance. Many strains of bacteria have evolved to resist antibiotics, over a few decades.
It’s not clear if Covid can evolve to fight Paxlovid. It might never happen. If it does happen, it will probably take decades.
There’s no reason to think that ivermectin would be any better or worse. Ivermectin doesn’t have multiple mechanisms of action. It has several hypothetical mechanisms of action, based on really sketchy computer models. It doesn’t share the same mechanism as Paxlovid, at any reasonable doses. It must have one other mechanism, because it works in vitro. And we have no good proof yet that it treats covid patients.
In summary:
Paxlovid looks like an excellent drug that will help cut down covid deaths.
It’s still too expensive, you probably won’t be able to get it if you’re under 65.
Vaccines remain the cheapest available treatment for covid.
Finding cheap drugs that treat covid is still an important goal.
John Campbell is either a misleading grifter or he just can’t do math. Unfortunately, a million people are watching this clown.
If you disagree, Dr Campbell, then underline the words you don’t like.
