One month ago, the Washington Post reported that the US government will purchase 10 million courses of Paxlovid, an antiviral Covid pill produced by Pfizer, for $5 billion.
As the administration and Pfizer on Tuesday hammered out the final details, the company asked federal regulators to authorizethe five-day antiviral pill regimen called Paxlovid. The medication is the second easy-to-take treatment aimed at keeping newly infected people out of the hospital to go before the Food and Drug Administration. The other is by Merck and Ridgeback Biotherapeutics.
In another important development, Pfizer has agreed to a license-sharing deal that would allow the pill to be manufactured around the globe and sold at lower prices in poor countries.
But the US government has to pay full price?
Maybe they want to pay full price.
It’s an agreement the company says could give more than half of the world’s population access to the treatment, even as Pfizer rebuffs calls to grant poorer countries access to its coronavirus vaccine formula.
Pfizer announced this month that Paxlovid, when given to people at high risk of severe illness within three days of symptom onset, reduced the rate of death and hospitalization by 89 percent. The clinical trial for the treatment was halted early because of overwhelming evidence that the medication worked.
It’s great that we finally have an effective early treatment option after nearly two years of Covid. Obviously remdesivir wasn’t getting it done.
The federal government already has committed to buy about 3.1 million courses of the Merck antiviral pill for approximately $2.2 billion, assuming the FDA authorizes the drug, the company has said. That comes to about $700 for each course of treatment. The government also has the option to buy an additional 2 million courses under that contract. An FDA advisory committee is scheduled to meet Nov. 30 to discuss the safety and effectiveness of molnupiravir.
Merck announced in October that its pill reduced the riskof hospitalization and death by nearly half among higher-risk people diagnosed with mild or moderate illness. Some scientists have raised questions about the safety of the Merck product because it inserts errors into the virus’s genetic code to prevent it from replicating. The concerns center on whether that could encourage mutations.
If it does, will they ever actually admit it?
Pfizer’s pill uses a different mechanism — an experimental molecule to block an enzyme that the coronavirus needs to make copies of itself. The Pfizer molecule must be given in combination with ritonavir, an antiviral drug used to treat HIV that helps slow the molecule’s breakdown.
The price for the Pfizer drug will be less than for the Merck pill — closer to $500 per treatment, said a federal official familiar with the negotiations, who spoke on the condition of anonymity because he was not authorized to discuss the issue. However, the details are not finalized, officials said.
Okay, so we’ve got this new but expensive treatment by Pfizer, and they’re saying all the trial data looks great; the government is on board, they’re ready to do this thing.
But people are already skeptical: “I’m sure it’s just Ivermectin at a 20x markup,” they’re saying.
Well, Dr. John Campbell, who has become one of my favorite people on YouTube, looked into the matter:
Dr. Campbell says that basically, Paxlovid is the same as Ivermectin.
He begins by explaining how viruses work when they get into your cells:
“When a virus, in this case SARS-CoV-2, gets into a cell, what happens is it starts making lots of proteins, and these proteins are ‘long proteins’. They’re made of hundreds, sometimes thousands, of amino acids, all strung together.
Now the problem with these long proteins is that they’re too long. It’s like a building site when a large shipment of wood arrives. It needs to be trimmed down into bits that fit in your door frames and window frames.
So these proteins need to be trimmed down. Now, how do we trim down a protein? Well, it has to be done in a biochemical way. The way it’s done, particulary with Covid, is there’s an enzyme called ‘3 CL protease.’ Protease is an enzyme which breaks down proteins–it’s what we call “proteolytic.” It will take these long proteins and chop them into shorter proteins, what we call endopeptidase.”
He gives a visual example. He has long pieces of paper to symbolize the long proteins, and a pair of scissors labeled “3 CL protease.” He uses the scissors to cut the long proteins into short proteins. The “CL” in 3 CL protease stands for “Chymotrypsin-like” protease, and a Chymotrypsin is an enzyme released by the pancreas to chop up proteins.
“Now these new drugs are what we call ‘protease inhibitors.’ They stop the protease from working,” Campbell says.
He then takes a piece of tape and wraps it around the tip of the scissors, making the scissors not work anymore. The protease inhibitor is the tape. It makes it so that the virus cannot break the long proteins down into the usable smaller proteins, and thus the virus cannot replicate.
Campbell then gets into a pharmacodynamic analysis, which basically looks at how a drug works and what it does to your body.
He shows us the shape of the molecule (C23,H32,F3,N5,O4)
He then shows us the Ivermectin molecule:
Now, I don’t know what this means or how to read this other than that the letters are elements on the Periodic table (Carbon, Hydrogen, Oxygen, Fluorine, Nitrogen) but the good doctor shows us that Paxlovid is a different molecule than Ivermectin.
But then he pulls up a study from the Royal Society of Chemistry called “Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection,” which says:
“The strength and persistency of the interaction between IVE [ivermectin] and the binding site of the 3CLprotease indicate that a partial inhibition of the catalytic activity could have a place as the drug interacts with the main subdomains that define the enzyme-binding pocket.”
Dr. Campbell points out that the protease is an enzyme.
So basically, Ivermectin has been shown to have the same effects of inhibiting the 3CL protease as Paxlovid does. It’s not the same drug, but it basically does the same thing in regard to Covid.
Campbell then pulls up another study, this one entitled “Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents.” What this study found was that:
“Out of 13 OTDs [off-target drugs, meaning a drug not originally intended for Covid] only ivermectin completely blocked (>80%) the 3CLpro activity.”
The study further states:
Emerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity.
So in the search for drugs that have the potential to be repurposed to fight Covid, Ivermectin was one of the more promising candidates. This study is from January 2021.
We now look at yet another study, this one has such a long and complicated name I don’t even feel like including it, so just hit the link for it. The study measured how well different drugs were able to “dock” with the 3CLpro enzyme, which means bind with it and inhibit it. This is what it found:
Novel inhibitor identification against the protein targets consists of evaluation of binding mode of interaction between inhibitor and receptor by performing molecular docking which assesses the effect of solvent on the protein–ligand complex stability. Molecular docking of ilimaquinone, hydroxychloroquine, azithromycin, favipiravir, ivermectin and remdesivir with nine potential SARS-CoV-2 target proteins was performed. Binding energies were calculated of the ligands against the protein targets. From the docking analysis, ivermectin showed the highest docking score with an average energy of −8.5 kcal mol−1 among all the compounds. Remdesivir showed the lowest binding energy and highest docking score of −9.9 kcal mol−1 which was followed by ilimaquinone having the second highest binding energy of −8.1 kcal mol−1. When compared with other protein targets, ilimaquinone showed second highest binding energy against 6M0J, PLpro, Nsp10 and Nsp14 targets with docking scores of −6.9, −8.1, −7.6 and −8.1 kcal mol−1. For 3CLpro, ilimaquinone exhibited similar binding energy of −7.1 kcal mol−1 as that of remdesivir and azithromycin. Whereas, for Nsp16, binding energies of ilimaquinone showed similarity with ivermectin and remdesivir. Ilimaquinone demonstrated lowest binding energy of −8.2 kcal mol−1 with Nsp13 among other protein targets.
So not only did it find Ivermectin was the best at binding to the 3CLpro enzyme, it found that remdesivir was the worst.
Which explains why you often hear reports that remdesivir doesn’t work despite its $2,000+ pricetag.
Dr. Campbell points out that ivermectin is available through the World Health Organization for 6 cents.
I think it’s important to point out that we who are interested in Ivermectin have no special attachment to Ivermectin itself inherently. It’s just that it’s the drug that comes up in so many studies as the one that works the best. You see these studies we’ve looked at, and Ivermectin seems to always come out on top. If it was ilimaquinone that consistently graded out top of its class, then we would be pushing for ilimaquinone.
But it’s not ilimaquinone. It’s ivermectin that consistently rates highly. And that’s why we like ivermectin.
By the way, it would seem to me that these studies, which show that ivermectin is highly effective at inhibiting the 3CLpro enzyme that enables the Covid virus to replicate, completely invalidate the idea that ivermectin only works because it gets rid of parasitic worms.
But I’m sure our buddy Gideon Myerowitz-Katz is on the way to “debunk” these studies on the grounds that they show a “high risk of bias.”
Let’s look at another study, “Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach.” In silico means, according to Dr. Campbell, computerized molecular modeling.
Aim: COVID-19 is currently the biggest threat to mankind. Recently, ivermectin (a US FDA-approved antiparasitic drug) has been explored as an anti-SARS-CoV-2 agent. Herein, we have studied the possible mechanism of action of ivermectin using in silico approaches. Materials & methods: Interaction of ivermectin against the key proteins involved in SARS-CoV-2 pathogenesis were investigated through molecular docking and molecular dynamic simulation. Results: Ivermectin was found as a blocker of viral replicase, protease and human TMPRSS2, which could be the biophysical basis behind its antiviral efficiency. The antiviral action and ADMET profile of ivermectin was on par with the currently used anticorona drugs such as hydroxychloroquine and remdesivir. Conclusion: Our study enlightens the candidature of ivermectin as an effective drug for treating COVID-19.
Dr. Campbell looks at a fifth study that also shows strong results for Ivermectin in inhibiting the 3CLpro enyzme. We won’t get into it too much because I think you get the picture by now, but here is the link for that study: “Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2.” This study showed that Ivermectin interferes with the virus’ spike protein so that it can no longer latch on to your ACE-2 and TMPRSS2 cell surface receptors. This means the virus can’t put its RNA into your cells.
The takeaway is that ivermectin fights the virus in multiple ways, and not just by inhibiting the 3CLpro enzymes the virus needs to replicate.
So what is the takeaway here? Dr. Campbell sums it up:
“Whereas the Pfizer drug is only working, as far as we’ve been told, against one biochemical modality of viral replication, Ivermectin is working at many different levels. Now the fact that the Pfizer drug is only working at one biochemical pathway means to me that the virus could learn to avoid that, it could evolve to be drug resistant. With Ivermectin, because it’s working on so many different levels, the idea that the virus would mutate in six different ways to dodge all of those, is improbable.
My message to world leaders: ‘Come on, y’all. Let’s use ivermectin to save human lives.’
And there you have it.
Not only does Ivermectin do the same thing Paxlovid claims to do to stop the virus, Ivermectin does even more, and it’s significantly cheaper.
One wonders if Pfizer designed Paxlovid to go after the 3CLpro enzymes after seeing the studies that show Ivermectin does just that.
I certainly hope Paxlovid works as an early treatment. We do not need to see more preventable deaths. But as Dr. Campbell noted, because Paxlovid is essentially a “one-trick pony,” there’s a chance–perhaps a strong chance–that the virus evolves to become resistant to Paxlovid.