447 replies to this topic

[Mind]

As another example of the completely bizarre, anti-science, and irrational attacks that occurred  during the COVID panic (and still ongoing), the Texas Medical Board still refers to Ivermectin as "dangerous".  Even if you ignore all of the RCT and observational evidence that ivermectin had a positive effect in the treatment of COVID, it is still one of the safest drugs ever and it has been prescribed billions of times around the world. Is the Texas Medical Board that dumb? Or do they just have a political/authoritarian axe to grind?

[Hip]

Why did that dumbo organisation the Front Line COVID-19 Critical Care Alliance (FLCCC) blatantly lie about ivermectin?

 

The FLCCC lied when they said here that "ivermectin, an anti-parasitic medicine, has highly potent anti-viral and anti-inflammatory properties against COVID-19."

 

In fact, ivermectin has no antiviral effects against COVID in vivo.

 

Why has the FLCCC being blatantly lying about ivermectin?

Edited by Hip, 17 March 2024 - 05:13 AM.

[Mind]

Just to re-iterate, the Texas Medical Board claims, in a court filing, that Ivermectin is dangerous. It is not. The Board is suppose to be an "authority", but like the CDC, they have abdicated their claim on authority by not following science at all. 

[Hip]

ivermectin has no antiviral effects against COVID in vivo

 

Two people have asked for references for this statement.

 

Well, here you go: this study finds that in vivo in the blood plasma of humans:

the free plasma concentration of ivermectin would be 250 times lower than the concentration required to reduce viral replication of SARS‐CoV‐2

 

In other words, not a hope in hell of ivermectin being antiviral in vivo. 

 

So why did the FLCCC lie about ivermectin being antiviral? 

[Advocatus Diaboli]

Re post #394

 

Selective editing is the hallmark of a tendentious mindset, and a weak unscientific mind such as yours, Hip.

 

You partially quote the study:

 

"the free plasma concentration of ivermectin would be 250 times lower than the concentration required to reduce viral replication of SARS‐CoV‐2"

 

The full quote of the sentence is:

 

"Considering both the total plasma concentration and protein binding, the free plasma concentration of ivermectin would be 250 times lower than the concentration required to reduce viral replication of SARS‐CoV‐2 in vitro (Figure 1)."

 

I have bolded and underlined the crucial part that Hip intentionally omitted in his attempt to cod the gull.

 

Note that the authors have made their required-concentration-needed-to-reduce-viral-replication-"in vivo" claim from an erroneous assumption that the in vivo concentrations have to be at least same as the in vitro concentrations in order to inhibit viral replication. A logical extrapolation which is unproven, and not addressed in their study.

 

However, it is clear that in studies cited by Mind et al., for example, there is clinical demonstration that ivermectin, indeed, does have in vivo anti-viral effects--as shown by the positive outcomes presented in those studies. 

 

"In other words, not a hope in hell of ivermectin being an antiviral in vivo (sic)". 

 

Wrong. 

Edited by Advocatus Diaboli, 18 March 2024 - 02:11 AM.

[Hip]

I have bolded and underlined the crucial part that Hip intentionally omitted in his attempt to cod the gull.

 
That's not the crucial part; the crucial part to note is that Advocatus Diaboli has a poor grasp of medical science.

 
Advocatus Diaboli may have mathematical expertise; and he may be good at online rudeness; but these skills do not necessarily translate into biology. 
 
 

Here is Advocatus Diaboli's mistake; he says:
 

Note that the authors have made their required-concentration-needed-to-reduce-viral-replication-"in vivo" claim from an erroneous unproven assumption that the in vivo and in vitro concentrations have to be at least same in order to inhibit viral replication. A logical extrapolation which is unproven, and not addressed in their study.

  
For Advocatus Diaboli's edification, this is not an unproven assumption; this is the standard way that you can estimate the potency of antiviral substances. 
 
You first measure what is called the EC50 or IC50 concentration of an antiviral substance in vitro, in a cell line. The EC50 is the concentration that will inhibit viral replication in a cell line by 50%. 
 
You then consult some pharmacokinetic studies, to see what sort of free concentrations of the substance can be obtained in the blood in vivo, when that substance is taken orally. To get a clinically useful effect, in the blood you normally have to exceed the EC50 concentration by at least 5 or 10 times. Preferably you want to exceed it 20 to 40 times to get a strong antiviral effect.
 
If you look the pharmacokinetics of commercial antivirals such as the herpes drug acyclovir, or antiretroviral drugs for HIV, you find that they may exceed the EC50 concentration by 20 to 40 times, which is why these are powerful antiviral drugs.
 
 
 

However, it is clear that in studies cited by Mind et al., for example, there is clinical demonstration that ivermectin does have in vivo anti-viral effects--as shown by the positive outcomes presented in those studies. 

  
Again a lack of understanding of medical science. 

 

A drug can have beneficial effects for a viral infection without actually being antiviral. One of the most effective drugs for seriously ill COVID patients in hospital is corticosteroids. These drugs have no antiviral effect (in fact they actually weaken the immune response, giving the virus a helping hand). However, corticosteroids tone down the immune attack on the lungs, which reduces collateral lung damage in the immune fight against the virus, and this increases survival chances for the patient. So just because a drug has positive outcomes for COVID, it does not prove it is an antiviral.

 

Ivermectin has at least two possibly beneficial mechanisms for severe COVID patients that I have previously covered, which may explain why in certain contexts, ivermectin can increase the chances of survival of COVID patients. But neither of those mechanisms are antiviral mechanisms.

 

 

 

Had the FLCCC been a bit smarter, and had they understood that ivermectin has no antiviral effects in vivo — but has other effects which might be beneficial for COVID — then the rest of the scientific community might have listened more. But the FLCCC kept talking about antiviral effects of ivermectin, which anyone who understands pharmacokinetics will know ivermectin does not have in vivo.

 

But the FLCCC were only doctors, and this is considered the lowest rung of medical science knowledge. 

 

 

 

 

Edited by Hip, 18 March 2024 - 02:03 AM.

[Advocatus Diaboli]

Re post # 396:

 

Regarding the first part of your post:

 

The translation of in vitro to in vivo effects doesn't account for hepatic metabolization of  a drug.  You don't get hepatic metabolization with in vitro analysis.

 

As for aciclovir, it's typically given as valaciclovir which is more bioavailable and converts to aciclovir after first pass hepatic metabolization. Which shows the importance of metabolites in gaging drug effectiveness. Hepatic metabolites aren't present in in vitro experiments.

 

Hip claims:

 

"A drug can have beneficial effects for a viral infection without actually being antiviral."

 

My assertion for ivermectin being antiviral is correct:

 

Look at definiton 3.

Edited by Advocatus Diaboli, 18 March 2024 - 03:18 AM.

[Dorian Grey]

I recall a doctor working in Africa describing how they had little more than an EKG & O-SAT monitors to work with, & HCQ & IVM for meds.  She seemed to like HCQ for outpatients, and would give IVM for patients who presented in bad shape.  Said she knew they were in trouble when O-SAT was low, & the pleth line of the O-SAT trace was muddy & weak.  

 

She said her overnight nurse would see the pleth line start bounding again once the patients had been on their IVM for 8-12 hours, & tell her "this one is ready to go" when she would come in the morning.  

 

Apparently IVM breaks up blood agglutination so it flows through capillaries better.  See attached: SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects

 

"IVM blocked HA when added to RBCs prior to spike protein and reversed HA when added afterward."

 

It may be HCQ is more valuable as an early treatment, and IVM especially helpful at salvage.  

Attached Files

•  IVMmechOfAction.pdf   2.43MB   2 downloads

Edited by Dorian Grey, 18 March 2024 - 02:42 AM.

[Hip]

My assertion for ivermectin being antiviral is correct:

 

Ever since I caught an enterovirus over 20 years ago which ruined my health, I have been studying virology, antiviral drug technology and immunology, in the hope of finding something that might treat my chronic enterovirus infection. Believe me, long before COVID came along, I learnt a few things about antivirals.

 

The word antiviral is a bit ambiguous: in the strictest sense, you might use this term to describe a substance which directly inhibits the viral lifecycle. In case you don't know, the viral lifecycle in brief is: break into a host cell; replicate tens of thousands of times within that cell; burst out of the cell, and let these thousands of newly created viral particles go off to infect more cells.  

 

There are several ways for antivirals to inhibit this viral lifecycle: 

• Antivirals can prevent the virus from attaching to the cell (attachment inhibitors)
• Antivirals can block viral entry into host cells (entry inhibitors)
• Antivirals can block the opening of the viral particle once inside the cell (uncoating inhibitors)
• Antivirals can reduce viral replication inside a host cell (replication inhibitors)
• Antivirals can stop the replicated viruses from leaving the cell (exit inhibitors)

And there are other antiviral mechanisms too.

 

All the above are direct antiviral mechanisms, which directly thwart or slow down the viral lifecycle.

 

However, some antivirals work indirectly, not by slowing down the viral lifecycle, but by boosting the immune response against the virus. Such antivirals would be better termed immunomodulators or immune boosters, as they modulate the immune response to better fight the virus, but they are often still referred to as antivirals.

 

Some drugs are actually a combination of a direct antiviral and an immunomodulator; they have two mechanisms that operate at the same time. Ribavirin, which is a somewhat toxic enterovirus antiviral, is an example of such dual action. It has antiviral effects for enterovirus, but also boosts the immune response against enteroviruses.

Edited by Hip, 18 March 2024 - 02:59 AM.

[Hip]

It may be HCQ is more valuable as an early treatment

 

Bear in mind that the pharmacokinetic analysis performed in this post showed that hydroxychloroquine has pretty much no antiviral effects in vivo. 

 

Now it may be that due to its zinc ionophore actions, HCQ combined with zinc has more antiviral effects than HCQ alone. Though I have not seen any in vitro studies examining the in vitro antiviral effects of the HCQ + zinc combo.

[Dorian Grey]

Bear in mind that the pharmacokinetic analysis performed in this post showed that hydroxychloroquine has pretty much no antiviral effects in vivo. 

 

Now it may be that due to its zinc ionophore actions, HCQ combined with zinc has more antiviral effects than HCQ alone. Though I have not seen any in vitro studies examining the in vitro antiviral effects of the HCQ + zinc combo.

 

Ralph Baric, arguably the godfather of all coronavirus research co-authored a paper on the zinc ionophore hypothesis, though his ionophore was not CQ/HCQ. 

 

https://www.ncbi.nlm...les/PMC2973827/

 

Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture

 

There has been debate about whether or not HCQ is eve a proper ionophore...  

 

https://www.longecit...inc-ionophores/

 

There are also other theories on why HCQ may be beneficial: 

 

The possible mechanisms of action of 4-aminoquinolines (chloroquine/ hydroxychloroquine) against Sars-Cov-2 infection (COVID-19):

 

Main biological activities of chloroquine (CQ) and hydroxychloroquine (HCQ) as anti-viral drugs.

Biological activity References

Inhibition of viral attachment and entry in the host cell

Inhibition of the biosynthesis of sialic acids

• inhibition of the N-glycosylation of the cell surface viral

receptor ACE2

• inhibition of the N-glycosylation of the viral spike (S) proteins

• inhibition of the synthesis of cell membrane sialic acids

 

Inhibition of PICALM expression and CME [15,16]

Endosomal alkalinization and inhibition of cellular endosomal

protease (cathepsin and/or TMPRSS2)

 

Inhibition of new viral particle maturation and spread

Endosomal alkalinization and inhibition of endosome-lysosome

membrane fusion

 

ERGIC and TGN vesicle alkalinization and inhibition of post-

translational modifications of viral proteins

 

ERGIC vesicle alkalinization and inhibition of viral budding [21]

Inhibition of p38 MAPK activation [23,24]

Inhibition of phospholipase A2 and membranous structures essential for replication and transcription

[Mind]

Not only is the Texas Medical Board spreading a completely false narrative about Ivermectin as "dangerous", most of the reporting about it have been false as well. Recall that Rolling Stone published an utterly ridiculous and false article claiming that Ivermectin overdoses were overwhelming Oklahoma hospitals. It never happened. A lot of people still think that most of the information they got from the media during the COVID panic was true, even though the fraud has been exposed over and over again. I wonder how many people still believe the fake study that was published in the Lancet regarding HCQ.

[Dorian Grey]

Of course the above possible mechanisms for CQ/HCQ didn't include inhibition of clotting and perhaps the most important effect of autoimmune attenuation.  

 

I wonder if anyone has studied whether or not those treated with HCQ have the same incidence of Long COVID?  

[Hip]

The person who marked by above pharmacokinetics post as "Ill Informed": would you kindly like to explain which area of my pharmacokinetic mathematical calculation you thought was wrong? Presumably you have expertise in pharmacokinetics, otherwise you would not have pressed the Ill Informed rating on such a mathematical post.

 

Of course the other explanation is that you are mindlessly pressing the Ill Informed button like a mad gibbon. But I like to think that you are genuine expert, so please enlighten us with your pharmacokinetic knowledge.

 

 

Edited by Hip, 19 March 2024 - 12:39 AM.

[Hip]

The translation of in vitro to in vivo effects doesn't account for hepatic metabolization of  a drug.  You don't get hepatic metabolization with in vitro analysis.

 

As for aciclovir, it's typically given as valaciclovir which is more bioavailable and converts to aciclovir after first pass hepatic metabolization. Which shows the importance of metabolites in gaging drug effectiveness. Hepatic metabolites aren't present in in vitro experiments.

 

In fact in vitro experiments can easily account for drugs metabolising into active metabolites. 

 

In cases where you have a prodrug which is metabolised into the active antiviral metabolite compound, such as valaciclovir metabolising into the active acyclovir, in vitro antiviral studies will typically use the active metabolite, whereas pharmacokinetic studies examining blood levels attained in human subjects will give prodrug orally to these subjects, but typically measure the blood levels of the active metabolite, not blood levels of the prodrug.

 

If blood levels of the (free) active metabolite can exceed the EC50 concentration value of the active metabolite determined by in vitro experiments, then you may have a viable antiviral on your hands.

 

 

So there is no difficulty in translating in vitro antiviral effects to in vivo when it comes to antiviral prodrugs, such as Valtrex, Valcyte and Famvir. All these three drugs are converted into their active metabolite in the body.

 

 

 

However, you cannot translate in vitro antiviral effects to in vivo when examining antiviral compounds which fight viruses not by a direct inhibition of the viral lifecycle, but by boosting immunity. Obviously, in vitro, you only have a cell line, and you don't have a full immune system present in the petri dish. So there is no way to model the effects of an immune boosting antiviral substance in vitro.

 

The only exception to this is antivirals which boost the intracellular immune system, that operates internally in cells. One such antiviral that activates intracellular immunity inside cells is interferon. In these cases, you can still model the immune boosting antiviral effect in vitro. But in general you cannot. 

 

So for antivirals which work via immune boosting, it is only live animal models that you can use to examine their efficacy. And of course human clinical trials.  

Edited by Hip, 19 March 2024 - 12:49 AM.

[Dorian Grey]

'Twas not I who dinged you Ill Informed mate, though it is frustrating when someone finds an angle supporting their narrative (HCQ is worthless), and proclaims it is proof the med is worthless.  

 

I had a doc on another forum point to a study showing HCQ did not prevent infection with coronavirus, forcing me to play whack-a-mole...  I'm trying to stay out of the hospital and off of a ventilator, and would prefer to live a few more years!  It matters not to me if it's not effective at preventing infection.   Hey, Paxlovid & the vaccines don't prevent transmission and infection either...  Does that mean they are worthless?  

[Hip]

'Twas not I who dinged you Ill Informed mate, though it is frustrating when someone finds an angle supporting their narrative (HCQ is worthless), and proclaims it is proof the med is worthless.  

 

I have no doubt it was not you.

 

But someone did. You'd think that people would only press the Ill Informed button when they know a sufficient amount about the subject. In this case, you would have to know about pharmacokinetics before you could claim someone's pharmacokinetic mathematics are ill informed. 

 

 

I am very interested in any cheap and well-tolerated antiviral that might work for SARS-CoV-2, because I am suffering from long COVID ME/CFS now, in addition to my original coxsackievirus B and cytomegalovirus ME/CFS. So I have three active viruses in my body, which makes it difficult to treat. 

 

If I can find an inexpensive and well-tolerated antiviral which works for any of my three viruses, then I may be able to improve my overall health. So this is why I have a big interest in searching for viable antivirals.

Edited by Hip, 19 March 2024 - 01:00 AM.

[joesixpack]

Why did that dumbo organisation the Front Line COVID-19 Critical Care Alliance (FLCCC) blatantly lie about ivermectin?

 

The FLCCC lied when they said here that "ivermectin, an anti-parasitic medicine, has highly potent anti-viral and anti-inflammatory properties against COVID-19."

 

In fact, ivermectin has no antiviral effects against COVID in vivo.

 

Why has the FLCCC being blatantly lying about ivermectin?

 

They did not lie. Ivermectin and Hydroxychloroquine were very effective against Covid. The are both safe and have been taken millions of times by humans.

 

HCQ was discovered to be effective against SARS 20 years ago, which led to the discovery during Covid that Ivermectin was also effective. They have to be given with zinc and a Zinc ionophore in order to be effective. As with Paxlovid they have to be taken within 5 days of the first symptoms.

 

As it turned out, Ivermectin was more effective against the Delta variant, while HCQ was more effective against Omicron.

 

Incidentally, since Paxlovid is now considered to be an effective treatment for Covid, why haven't the vaccine EUA's been withdrawn?

[joesixpack]

I have no doubt it was not you.

 

But someone did. You'd think that people would only press the Ill Informed button when they know a sufficient amount about the subject. In this case, you would have to know about pharmacokinetics before you could claim someone's pharmacokinetic mathematics are ill informed. 

 

 

I am very interested in any cheap and well-tolerated antiviral that might work for SARS-CoV-2, because I am suffering from long COVID ME/CFS now, in addition to my original coxsackievirus B and cytomegalovirus ME/CFS. So I have three active viruses in my body, which makes it difficult to treat. 

 

If I can find an inexpensive and well-tolerated antiviral which works for any of my three viruses, then I may be able to improve my overall health. So this is why I have a big interest in searching for viable antivirals.

 

You might want to try the FLCCC's long Covid protocol. Interesting isn't it? While most of the medical community was denying that Long Covid existed, back in the day, these guys did not deny it. Rather, as front line physicians, they worked out a way to treat it.

 

You can find it here: https://covid19criti...ovid-treatment/

[Hip]

They did not lie. Ivermectin and Hydroxychloroquine were very effective against Covid. The are both safe and have been taken millions of times by humans.

 

The question is not whether ivermectin is effective for COVID. The issue I raised is whether it is antiviral for SARS-CoV-2 in vivo. The answer is that ivermectin has no antiviral effects in vivo. Although in order to appreciate this fact, you will need to understand the simple mathematics I outlined in early posts (namely that ivermectin blood levels are 250 times too low to achieve any antiviral efficacy). I appreciate this may be beyond the mathematical abilities of some people here. 

 

So when the FLCCC said that ivermectin is antiviral, they lied.

 

Edited by Hip, 19 March 2024 - 04:50 AM.

[Hip]

You might want to try the FLCCC's long Covid protocol. Interesting isn't it? While most of the medical community was denying that Long Covid existed, back in the day, these guys did not deny it. Rather, as front line physicians, they worked out a way to treat it.

 

You can find it here: https://covid19criti...ovid-treatment/

 

Thanks for that link to FLCCC long COVID treatments. Though I've tried pretty much everything on their list, and other things too, without observing much benefit. 

 

The FLCCC once again state in your link that ivermectin is antiviral, which it is not.

 

Remember that the FLCCC are doctors, and doctors are the lowest rung on the hierarchy of medical intelligence. This is why they make silly mistakes like claiming ivermectin is antiviral. If they cannot get that right, what other mistakes might the FLCCC be making?

 

 

I know people with long COVID who have temporarily improved a bit from taking ivermectin at 15 mg daily; but I suspect this is a result of the anti-inflammatory effect of ivermectin. Unfortunately as soon as they stop ivermectin, their symptoms worsen again.

Edited by Hip, 19 March 2024 - 04:47 AM.

[joesixpack]

A new study in the UK finds people who took Ivermectin did better.

 

Here is the article: https://www.gulf-ins...ff-study-finds/

[Dorian Grey]

The question is not whether ivermectin is effective for COVID. The issue I raised is whether it is antiviral for SARS-CoV-2 in vivo. The answer is that ivermectin has no antiviral effects in vivo. Although in order to appreciate this fact, you will need to understand the simple mathematics I outlined in early posts (namely that ivermectin blood levels are 250 times too low to achieve any antiviral efficacy). I appreciate this may be beyond the mathematical abilities of some people here. 

 

So when the FLCCC said that ivermectin is antiviral, they lied.

 

Splitting hairs Hip.  IVM may not be "virucidal" to SARS-CoV-2, but if it counteracts the agglutination/clotting caused by the virus which is what sends patients to hospital/morgue, might it not be considered anti-viral, in that it halts the viral morbidity that might otherwise be caused by the virus?  

 

I'm a simple man, and if there is a viral plague that is sending seniors to the hospital, where they are put on a vent to die, and someone finds a drug that ameliorates this...  I'd call that anti-viral!  

 

I learned a new term...  Sealioning, which may apply: https://en.wikipedia...wiki/Sealioning

 

Sealioning (also sea-lioning and sea lioning) is a type of trolling or harassment that consists of pursuing people with relentless requests for evidence, often tangential or previously addressed, while maintaining a pretense of civility and sincerity ("I'm just trying to have a debate")

Attached Files

•   TheTerribleSeaLion.pdf   954.29KB   4 downloads

Edited by Dorian Grey, 19 March 2024 - 05:29 AM.

[Hip]

Splitting hairs Hip.  IVM may not be "virucidal" to SARS-CoV-2, but if it counteracts the agglutination/clotting caused by the virus which is what sends patients to hospital/morgue, might it not be considered anti-viral, in that it halts the viral morbidity that might otherwise be caused by the virus?  

 

It's not splitting hairs really. Any medical scientist who understands pharmacokinetics will appreciate that ivermectin is not antiviral for SARS-CoV-2 in vivo.

 

So when the ivermectin evangelists were touting this drug as a good COVID antiviral during the pandemic, scientists were ignoring them, because these scientists are aware that ivermectin cannot be antiviral. 

 

Thus the fatal mistake that the evangelists made was to promote ivermectin as an antiviral. Had the evangelists instead promoted ivermectin as an anti-inflammatory, or an immunomodulator, then scientists might have listened to them. 

[Dorian Grey]

Antiviral in that it counteracts the effects of the virus?  Sealioning!  

Attached Files

•  sealion.jpg   1.12MB   0 downloads

Edited by Dorian Grey, 19 March 2024 - 05:48 AM.

[Hip]

Antiviral in that it counteracts the effects of the virus?  

 

Well, if you are going to count that as an antiviral, then by the same token, you might count a drug that causes girls to get ugly outbreaks of acne a contraceptive! 

Edited by Hip, 19 March 2024 - 05:57 AM.

[joesixpack]

Well, you are free not to take it. It worked for us, but if you feel it is not worth trying because. someone told you it was wrong, that is you choice. Good night.

[Advocatus Diaboli]

Re: #416:

 

Ho, hum. Once again, Hip, ivermectin is, by definition (see #3), an antiviral.

 

 

[Hip]

Re: #416:
 
Ho, hum. Once again, Hip, ivermectin is, by definition (see #3), an antiviral.

 

With the definition of an antiviral you use: "inhibiting the effectiveness of viruses", almost anything could be an antiviral. A subscription to Netflix would be an antiviral by your definition, if it keeps someone at home watching movies instead of going out socialising and being exposed to respiratory viruses. 

 

 

[Hip]

So we go back to the fact that the FLCCC lied about ivermectin being antiviral.