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Thread: Interesting Video

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    Senior Member dneal's Avatar
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    Senior Member dneal's Avatar
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    Default Re: Interesting Video

    DAMNING THE SOURCE: (ad hominem, sometimes called the genetic fallacy) attempts to refute an argument by indicting the source of the argument, rather than the substance of the argument itself. Attacking the messenger, not the message.
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    Default Re: Interesting Video

    The addition of an effective antiviral to the arsenal fighting Covid pandemics is welcome. I don't see any reason for disputation over this. Let's get 10 more anti-virals, if they work!

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    Senior Member dneal's Avatar
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    Default Re: Interesting Video

    Not sure if you meant to post this here or in the vaccine question thread…

    Anyway, I agree that drugs that inhibit 3CL protease and therefore effectively combat Covid are welcome. Some seem to disagree, depending on the drug.
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    Default Re: Interesting Video

    ?? I'm responding to your video. I watched the first 3 minutes (my limit) and I know what it is about. Again, I welcome any new effective weapons (I am assuming that they are safe, additionally, etc, etc).

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    Senior Member dneal's Avatar
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    Default Re: Interesting Video

    No problem. Your post works in response to kazoolaw’s NIH article too, hence my question…. Thanks for taking the time to watch.
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    Default Re: Interesting Video

    Somebody has time to sit around and watch YouTube all day. LOL!! Funny how many old men spend their lives this way. @tsherbs, just don't do this when you retire.

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    Senior Member dneal's Avatar
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    Default Re: Interesting Video

    Alternate version: "Somebody has time to sit around and post inane fallacies all day." Hypocrisy, while not a fallacy of thinking; does undermine credibility.

    It is an ad hominem: “against the man,” and this type of fallacy is sometimes called name calling or the personal attack fallacy. This type of fallacy occurs when someone attacks the person instead of attacking his or her argument.

    Also included is an appeal to ridicule: The fallacy uses this claim in an attempt to invalidate the argument since it is not worth entertaining (informally called "horselaugh"); culminating in a Red Herring: a rhetorical device that diverts attention from the topic-at-hand.
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    Senior Member dneal's Avatar
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    Default Re: Interesting Video

    Dr. Campbell changed the title of his video. I assume the initial "Interesting Video" title was to bypass YouTube's censorship algorithm, but who knows. It is now titled New Pfizer drug and ivermectin

    From the description:

    Quote Originally Posted by Dr. John Campbell
    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

    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)

    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

    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

    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

    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

    Ritonavir, C37H48N6O5S2

    Ivermectin, C48H74O14

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

    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

    Risk of virus developing resistance to PF-07321332

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

    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
    Layman's summary:
    - Pfizer (and others) are developing new molecules that inhibit the 3CL protease.
    - 3CL inhibitors already exist - one of them being ivermectin.
    - Ivermectin is out of patent, and costs pennies per dose.
    - Drugs still in patent (e.g.: Remdesivir) are exponentially expensive, with costs varying by country.

    So, as ethernautrix posits: "Is it immoral to ask, Follow the money (question implied)?"

    The moral question(s) I have revolves around the concerted effort to demonize a cheap and apparently very effective drug used (in concert with others) to treat COVID? How many deaths could have been prevented?
    Last edited by dneal; November 11th, 2021 at 07:28 AM. Reason: fixed link
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    Default Re: Interesting Video

    The sales performance was in sharp contrast to Pfizer, which raised its outlook for its vaccine for a second time this year. Pfizer expects to generate $36 billion in vaccine sales this year, accounting for as much as 44 per cent of its total sales, having upgraded forecasts from $33.5 billion in July and $15 billion in February.
    The two companies are becoming dominant in the Covid-19 vaccine market, partly due to the high efficacy, despite both having complicated and costly cold storage systems.
    Moderna expects to deliver between 700 million and 800 million doses, compared to between 800 million and one billion as previously forecast.
    It has forecast sales of $17 billion to $22 billion next year as it signs deals with more countries and booster doses.


    Pharmaceutical patent disputes were rarely mainstream matters before the coronavirus, but the current fight between Moderna and the National Institutes of Health over their weirdly named Spikevax shot is a title bout with major implications regarding how the vaccine could be distributed worldwide.
    While last year the government was calling the shot the “NIH-Moderna COVID-19 vaccine,” the biotech giant filed a patent made public this week in which it found that “only Moderna’s scientists” designed the vaccine. The patent, filed in July, is specific to the genetic sequence creating spike proteins, which allow vaccine recipients to build antibodies to block the virus when the body is actually exposed. As the New York Times reports, the NIH was surprised by the attempt at a solo effort. If the two parties cannot figure out a way to split the credit, the government will have to determine if it will take the expensive step of going to court. Already, the U.S. has paid $10 billion in taxpayer funds for Moderna to help create the vaccine, test its efficacy, and provide shots for the federal government. The Biden and Trump administrations also purchased $35 billion worth of vaccines to be produced through the end of next year.
    The ownership of the patent also carries serious ramifications for the distribution of shots amid a pandemic in which G20 members still have 15 times more vaccine access than sub-Saharan nations. “Patents are development monopolies, and in a pandemic it is a terrible idea to have a private corporation have a monopoly on part of a lifesaving technology,” drug-policy expert Zain Rizvi told the Times. And while Moderna has promised not to enforce its COVID patents during the pandemic, if the NIH were deemed co-inventors of the vaccine, that would allow the government to maintain more direct involvement in the production of the vaccine even when the pandemic subsides.
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    Default Re: Interesting Video

    Bump for Lady Ethernaut, since she's about.
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    Default Re: Interesting Video

    "Conclusion
    Previous experimental studies demonstrated that IVM could inhibit SARS-CoV-2 replication in vitro; however, IVM's molecular mechanism inhibits binding to importin-α, and other SARS-CoV-2 receptors have not yet been elucidated. Recently, docking studies suggested the possible molecular mechanism through which IVM could inhibit mouse importin-α and some key SARS-CoV-2 targets (Nsp9 replicase, RdRp, and Nsp13 helicase), paving the way to the development of more robust studies. In this research, we explored the ability of IVM to inhibit human importin-α and five SARS-CoV-2 targets: dimeric 3CLpro, Nsp9 replicase, Nsp13 helicase, RdRp, and RBD-spike protein, using docking analysis, MD simulations coupled to the MMGBSA approach, and per-residue decomposition analysis. Hydrophobic and hydrophilic interactions guided interactions between IVM and importin-α, dimeric 3CLpro, and Nsp9, hydrophilic interactions being more critical for IVM binding at the central binding groove of importin-α. Per-residue free energy analysis let us identify hot-spot residues for importin-α-IVM (Trp184, Asn188, Arg227, and Trp231), 3CLpro-IVM (His41, Met49, Leu50, Leu141, Asn142, Met165, Glu166, and Gln189), and Nsp9-IVM (Leu4, Pro6, Leu97, Arg99, Gly100, Met101, Leu103, and Gly104), which contribute significantly to the affinity. MMGBSA results revealed that dimeric 3CLpro has the highest relationship among the different COVID-19 targets, followed by importin-α and Nsp9, which showed similar IVM affinity. This result indicates that the inhibitory activity of IVM maybe by targeting IMP and two essential targets of SARS-CoV2 (dimeric 3CLpro and Nsp9).

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054936/


    For @dneal, elucidate means to make clear.

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    Senior Member dneal's Avatar
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    Default Re: Interesting Video

    You should read the rest of the paragraph - or even the sentence that follows what you bolded. You don't like quoting out of context, after all.

    --edit--

    I forgot the importance of definitions. Maybe this may help. Pay particular attention of their use in the bolded sentence and the one that immediately follows.

    Previous: adjective. 1. Existing or occurring before in time or order. 2. Overly hasty in acting or in drawing a conclusion.
    Recently: adverb. At a recent time; not long ago.
    Last edited by dneal; November 25th, 2021 at 09:51 AM.
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    Default Re: Interesting Video

    The only important thing that needs to said is none voting for military is not supported by military leaders. It is also not supported as responsible citizenship in a democracy.

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    Default Re: Interesting Video

    Chuck, you're in the wrong thread. We're arguing voting in a different one.

    This is the thread where you completely shot yourself in the foot with the NIH article you cited.

    Maybe the blood loss is the cause of the confusion
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