Pfizermectin vs Ivermectin: Pf-1-Mode vs. Iver-several Modes

Here’s 2 rather great news videos from Dr. John Campbell. The first one comes after the second one (which it references) but IMHO is important enough to watch first (just in case EwTube decides it has too much actual science and evidence in it and so must be banned with all the other Banned Truths…)

It compares Pfizermectin mode of action with Ivermectin modes of action and finds that (as far as we know) they share one mode (blocking of 3CL-Protease) while Ivermectin also blocks the Spike Protein, the ACE2 receptor site, and a few other things the virus needs. IMHO a “must watch” for anyone seeking therapeutics or considering what to take. It does look like Pfizermectin will work, so I’d not refuse it were it the drug on offer.

Has interesting “denial of what happened to say just what happened” in a place or two ;-)

The text from the video with links to references. Note that I’ve removed the EwTube redirect tracking junk from these links, but IFF I’ve messed one up, you can try the “track me” link in the video text:

Dr. John Campbell
1.28M subscribers
New Pfizer antiviral and ivermectin, a pharmacodynamic analysis

New Pfizer antiviral, PF-07321332, C₂₃H₃₂F₃N₅O₄

PF-07321332 is designed to block the activity of the SARS-CoV-2-3CL protease,

https://www.pfizer.com/news/press-release/press-release-detail/pfizers-novel-covid-19-oral-antiviral-treatment-candidate

So, what is a protease?

So what is a protease inhibitor?

And, what is 3CL?

Chymotrypsin-like protease (3CL main protease, or 3CL Mpro)

Identification of SARS-CoV‑2 3CL Protease Inhibitors by a Quantitative High-Throughput Screening (3rd September 2020)

https://pubs.acs.org/doi/abs/10.1021/acsptsci.0c00108#

The activity of the anti-SARS-CoV-2 viral infection was confirmed in 7 of 23 compounds

Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection

https://pubs.rsc.org/en/content/articlehtml/2021/cp/d1cp02967c

the strength and persistency of the interaction between IVE and the binding site of 3CLpro indicate that a partial inhibition of the catalytic activity could have place as the drug interacts with the main subdomains that define the enzyme binding pocket:

Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

https://www.nature.com/articles/s42003-020-01577-x

as shown in Fig. 4, out of 13 OTDs only ivermectin completely blocked ( more than 80%) the 3CLpro activity at 50 µM concentration.

Development, validation, and approval of COVID-19 specific drugs takes years. Therefore, the idea of drug repositioning, also known as repurposing, is an important strategy to control the sudden outbreak of life-threatening infectious agents that spread rapidly.

Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study

https://pubs.rsc.org/en/content/articlehtml/2020/ra/d0ra06379g

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

(Only works in the U.K. and redirects to a nag link for me, so to see it be in the UK – E.M.S.)

https://bnf.nice.org.uk/medicinal-forms/remdesivir.html

Ritonavir, C37H48N6O5S2

Ivermectin, C48H74O14

Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7996102/

We have documented an intense binding of both ivermectin B1a and B1b isomer to the main protease with subsequent energy (ETot-) values of -384.56 and -408.6.

PF-07321332 is designed to block the activity of the SARS-CoV-2-3CL protease,

https://www.pfizer.com/news/press-release/press-release-detail/pfizers-novel-covid-19-oral-antiviral-treatment-candidate

Risk of virus developing resistance to PF-07321332

Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2

https://www.frontiersin.org/articles/10.3389/fmicb.2020.592908/full

With SARS-CoV-2 S Spike protein

Ivermectin showed high binding affinity to the viral S protein as well as the human cell surface receptors ACE-2 and TMPRSS2.

In agreement to our findings, ivermectin was found to be docked between the viral spike and the ACE2 receptor

Binding Interactions of Selected Drugs With Human TMPRSS2 Protein (ACE2 protein)

The docking results revealed that ivermectin showed the highest binding affinity to the active site of the protein (MolDock score −174.971) and protein–ligand interactions

Binding Interactions of Selected Drugs With Human ACE-2 Protein

that ivermectin showed the highest binding affinity to the active site of the protein (MolDock score −159.754) and protein–ligand interactions

With SARS-CoV-2 S Glycoprotein

Ivermectin showed the highest binding affinity to the predicted active site of the protein

With SARS-CoV-2 Nsp14 Protein

ivermectin showed the highest binding affinity (MolDock score −212.265) and protein–ligand interactions

Binding Interactions of Selected Drugs With SARS-CoV-2 PLpro

Ivermectin showed the highest binding affinity to the predicted active site of the protein (MolDock score −180.765) and protein–ligand interactions

A brief message to world leaders

Come on ya all

This second video is from the day before the top one, and is largely just the announcement of Pfizermectin and the Pfizer Hype about how great it is. It likely IS good at blocking the 3CL Protease enzyme as they were likely able to “tune it up” for just that mode. But in the context of the above studies you can see what they gave up for that enhanced single mode. It also covers several other drugs and compares their effectiveness:

Highly effective new antiviral
313,490 viewsNov 7, 2021

Dr. John Campbell
1.28M subscribers

Protectors from hospitalization, the story so far. Link to free download John’s 2 textbooks
http://159.69.48.3/

Oral meds than can be prescribed from home with onset of symptoms

Molnupiravir, approved by MHRA

https://www.gov.uk/government/news/first-oral-antiviral-for-covid-19-lagevrio-molnupiravir-approved-by-mhra

The antiviral was found to be safe and effective following a stringent review of the available evidence.

https://www.merck.com/news/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-by-approximately-50-percent-compared-to-placebo-for-patients-with-mild-or-moderat/

Public domain data, Merck press release

$ 700 per 5-day course

Under 50% reduction in deterioration

Effect of early treatment with fluvoxamine

Together Trial group

Public domain data, Peer reviewed trial in the Lancet

https://clinicaltrials.gov/ct2/show/NCT04727424

https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext

Adults with a risk factor

$4 for a 10-day course

32% protection against hospitalization

32% protection against death

Fluvoxamine is approved by the Food and Drug Administration as an antidepressant

Doctors already can prescribe it off-label — using their clinical judgment
https://www.washingtonpost.com/science/2021/10/28/antidepressant-fluvoxamine-coronavirus-lancet/

(This one also only works in the U.K. and redirects to a nag link for me, so to see it be in the UK – E.M.S.)

https://bnf.nice.org.uk/drug/fluvoxamine-maleate.html

https://www.togethertrial.com/

Ivermectin, Together trial results not yet released

PFIZER’S NOVEL COVID-19 ORAL ANTIVIRAL TREATMENT CANDIDATE REDUCED RISK OF HOSPITALIZATION OR DEATH BY 89% IN INTERIM ANALYSIS OF PHASE 2/3 EPIC-HR STUDY

https://www.pfizer.com/news/press-release/press-release-detail/pfizers-novel-covid-19-oral-antiviral-treatment-candidate

Public domain data, Pfizer press release

PAXLOVID™ (PF-07321332; ritonavir)

Found to reduce the risk of hospitalization or death by 89%

Compared to placebo in non-hospitalized high-risk adults with COVID-19

Through Day 28

PAXLOVID group

No deaths

Placebo group

10 deaths

Pfizer plans to submit the data as part of its ongoing rolling submission to the U.S. FDA for Emergency Use Authorization (EUA) as soon as possible

Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients)

Randomized, double-blind study of non-hospitalized adult patients with COVID-19,

who are at high risk of progressing to severe illness

Scheduled interim analysis

89% reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo

In patients treated within 3 days of symptom onset

PAXLOVID group

0.8% of patients hospitalized

3/389 hospitalized with no deaths

Placebo group

7.0% of patients hospitalized or died

27/385 hospitalized

with 7 subsequent deaths

(p less than 0.0001) 1 in 10,000 chance

In patients treated within 5 days of symptom onset

PAXLOVID group

1.0% of patients hospitalized

6/607 hospitalized with no deaths

Placebo group

6. 7% of patients hospitalized or died

41/612 hospitalized,

with 10 subsequent deaths

p less than 0.0001

At the recommendation of an independent Data Monitoring Committee and in consultation with the U.S. Food and Drug Administration (FDA), Pfizer will cease further enrollment into the study

due to the overwhelming efficacy demonstrated in these results

About the Phase 2/3 EPIC-HR Study Interim Analysis

1,219 adults enrolled out of 3,000 planned

North and South America, Europe, Africa, and Asia

Enrolled individuals had a laboratory-confirmed diagnosis of SARS-CoV-2 infection

Mild to moderate symptoms

At least one characteristic or underlying medical condition

Randomized (1:1) to receive PAXLOVID™ or placebo orally every 12 hours for five days

About the Phase 2/3 EPIC-HR Study Safety Data

Safety data, n = 1881

Treatment-emergent adverse events

PAXLOVID™group

19%

Placebo group

21%

Most of which were mild in intensity

Fewer serious adverse events

PAXLOVID™group

1.7%

Placebo group

6.6%

Discontinuation of study drug due to adverse events

PAXLOVID™group

2.1%

Placebo group

4.1%

Pharmacology

Specifically designed SARS-CoV-2-3CL protease inhibitor,

an enzyme that the coronavirus needs to replicate

Co-administration with a low dose of ritonavir helps slow the metabolism of PF-07321332

PF-07321332 inhibits viral replication at a stage known as proteolysis,

which occurs before viral RNA replication

In preclinical studies, PF-07321332 did not demonstrate evidence of mutagenic DNA interactions.

EPIC-SR includes a cohort of vaccinated patients who have an acute breakthrough symptomatic COVID-19 infection and who have risk factors for severe illness.


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About E.M.Smith

A technical managerial sort interested in things from Stonehenge to computer science. My present "hot buttons' are the mythology of Climate Change and ancient metrology; but things change...
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13 Responses to Pfizermectin vs Ivermectin: Pf-1-Mode vs. Iver-several Modes

  1. E.M.Smith says:

    Related article:

    https://www.fiercebiotech.com/biotech/pfizer-s-oral-covid-19-antiviral-cuts-hospitalization-death-by-85-sending-team-barreling-to

    Biotech
    UPDATE: Pfizer’s oral COVID-19 antiviral cuts hospitalization, death by 85%, sending team barreling to FDA
    by Nick Paul Taylor | Nov 5, 2021 7:41am

    Pfizer’s oral COVID-19 antiviral Paxlovid has cut the risk of hospitalization or death by 85% in a late-phase trial, prompting the Big Pharma to stop the study and race to seek emergency use authorization from the FDA.

    Merck showed oral antivirals can make a difference in COVID-19 around one month ago, presenting late-phase data showing its candidate halved the risk of hospitalization and death. Comparing results from different studies can give a misleading impression, but, on the surface, it appears Pfizer may have reset expectations of efficacy for oral antivirals.

    Pfizer’s phase 2/3 trial randomized non-hospitalized adult COVID-19 patients who were at high risk of progressing to severe illness to receive placebo or Paxlovid, a combination of the protease inhibitors PF-07321332 and ritonavir. The efficacy analysis is based on 1,219 patients.

    There were six hospitalizations and no deaths among the 607 patients who received Paxlovid within five days of symptom onset, compared to 41 hospitalizations and 10 deaths in the placebo cohort. The rates of hospitalization or death in the Paxlovid and control arms were 1% and 6.7%, respectively, resulting in a risk reduction of 85%.
    […]

    Pfizer used data on patients who were treated within three days of symptom onset as the headline finding in its press release
    . In that subpopulation, the rates of hospitalization or death in the Paxlovid and control groups were 0.8% and 7%, respectively, resulting in a risk reduction of 89%. Merck’s 50% reduction was seen in patients who were randomized within five days of symptom onset.

    I want to see the study on Ivermectin on “patients who were treated within three days of symptom onset” (instead of the crap studies where they only give it after virus replication is completed and you are hospitalized in the cytokine storm phase…)

  2. jim2 says:

    We are about to see some leftard heads explode :) That’s a good thing.

  3. cdquarles says:

    Good to see them working on other therapeutics. Bad for them to bad-mouth others that have been around for so long. (Wish I could add sarcasm)

  4. tom0mason says:

    From https://retractionwatch.com/2021/11/09/bad-math-covid-treatment-paper-by-pierre-kory-retracted-for-flawed-results/
    Due to mistakes, a study of Ivermectin has been retracted.

    Bad MATH+? Covid treatment paper by Pierre Kory retracted for flawed results
    The article has been retracted after the journal received notice from Sentara Norfolk General Hospital in Norfolk, Virginia (“Sentara”) raising concerns about the accuracy of COVID-19 hospital mortality data reported in the article pertaining to Sentara. Sentara’s notice included the following statements:

    ‘The data from Sentara Norfolk General Hospital were presented in Table 2, which lists in-hospital or 28-day mortality rates at the 2 MATH+ centers as compared to 10 published single-center and multicenter reports. The mortality rate among 191 patients at Sentara Norfolk General Hospital as of July 20, 2020 was reported as 6.1%, as compared to mortality rates reported in the literature ranging from 15.6% to 32%. The authors state that these data

    “provide supportive clinical evidence for the physiologic rationale and efficacy of the MATH+ treatment protocol.”‘

  5. beththeserf says:

    Compelling video by Dr Campbell- analysis of Ivermectin studies, high docking of Covid Virus using the scissor analogy and 3cl protease. It’s main problem remains that it is too cheap to appeal to Big Pharma of course.

  6. YMMV says:

    Good video. risqué for YT.

    From a comment there:
    3CL protease inhibition is a tidy way of tying ivm to a “legit” treatment discussion

  7. Lynn Clark says:

    After I sent a link to my brother to the Dr. Campbell “Interesting Video” where he goes over all the studies showing IVM efficacy, my brother pointed out that all of the studies were published between about 8-14 months ago. As my brother said, “Maddening.”

  8. AC Osborn says:

    tom0mason says: 9 November 2021 at 11:31 pm

    Apparently they did not include patient’s deaths when they died after the end of the study period.

    They also stated that not all the patients were actually using the study protocol, so who informed them that they were?

  9. Dave says:

    “If approved as a covid-19 treatment, ivermectin could even threaten the emergency use authorization granted to covid-19 vaccines. One of the basic conditions for the emergency use authorization granted to the vaccines currently being used against covid is that there are no alternative treatments available for the disease. As such, if ivermectin or some other promising medicine such as fluvoxamine were approved as an effective early treatment for Covid-19, the vaccines could be stripped of authorization.” Prescription Politics exposed!

  10. another ian says:

    “Do I help thee? Let me count the ways!”

    “How many mechanisms do you need? Ivermectin protects us from Covid in 20 ways”

    https://joannenova.com.au/2021/11/how-many-mechanisms-do-you-need-ivermectin-protects-us-from-covid-in-20-different-ways/

  11. another ian says:

    More on that – retracted BUT in comments!

    “red edwards
    November 12, 2021 at 5:08 am · Reply
    Well, the Editor-in-Chief has retracted the article.

    ” Postpublication review confirmed that while the review article appropriately describes the mechanism of action of ivermectin, the cited sources do not appear to show that there is clear clinical evidence of the effect of ivermectin for the treatment of SARS-CoV-2.”

    However. . .

    “None of the authors agreed to the retraction.”

    Reads like somebody decided this was TMI (too Much Information) and should be muzzled. Who did the leaning on the Editor-In-Chief is left to the reader’s digression. . . .”

    AND

    “Just being courteous, Jo; from one old Microbiologist to another.

    The phrasing of the retraction sounds like the editor didn’t really want to retract it, but was required to. One doesn’t normally say the data/work is good, but, but the cited sources weren’t acceptable. Usually the work itself is described as inadequate in some manner, in a retraction, and usually the authors themselves request the retraction.

    Make of it what you will. . .”

  12. another ian says:

    FWIW

    “Via Conservative Beaver
    Wife of Pfizer’s CEO dies after complications from the vaccine.
    https://www.conservativebeaver.com/2021/11/10/the-wife-of-pfizers-ceo-dies-from-complications-from-the-vaccine/

    http://www.smalldeadanimals.com/2021/11/12/november-12-2021-reader-tips/#comment-1532168

    And subsequent comments re confirmationj

  13. AC Osborn says:

    Ian, apparently untrue, beaver are accused of making stuff up.

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