Gates Foundation to spend $120 mil on access for COVID-19 pill

Stupid space flights indeed. At least Gates has always used his money and cared about this planet! Can't really say the same about the other billionaires out there.

Why should we risk taking this expensive drug when we have available a safe and cheap drug that is at least as effective as molnupiravir.

It's mostly about the money. Sort of.

It's mostly about the money. Sort of.

Yes, at the expense of our health...

Serious concerns have been raised with molnupiravir. This new drug is a nucleoside analog that causes mutations in the viral replication; this will likely result in an increase in the appearance of variants. Some have also expressed concerns, supported by animal studies, that this mutagen may increase mutations in the host (the patient). I'm guessing that this would be from conversion of the nucleoside to the corresponding deoxynucleoside, which would cause mutations when introduced into the host's DNA.

Further tests are required, we should not just rely on Merck’s press release…

It's mostly about the money. Sort of.

Except when it is not, but the science. Unfortunately antiscientific people will look for any kind of excuse to reject scientific knowledge and make up fake conspiracies where doctors and nurses deny supposedly effective drugs to their patients, friends and family just so other people can get rich, which makes no sense at all.

Yes, at the expense of our health...

That applies much more to politicians that use completely ineffective drugs for political gain instead of doing what has been repeatedly proved as effective, even if economically and politically expensive, Brazil being a prime example.

Serious concerns have been raised with molnupiravir. This new drug is a nucleoside analog that causes mutations in the viral replication; this will likely result in an increase in the appearance of variants.

That "theory" has no scientific value, because nucleoside analogs are not necessary for RNA viruses to be constantly mutating nor the mutations are in any way more likely to result in better adaptation but the opposite.

Some have also expressed concerns, supported by animal studies, that this mutagen may increase mutations in the host (the patient). I'm guessing that this would be from conversion of the nucleoside to the corresponding deoxynucleoside, which would cause mutations when introduced into the host's DNA.

Fortunately your "guess" is based on complete ignorance of nucleotide based biology, the patients cells do not convert RNA to DNA, nor any cytoplasmic DNA has a way to go into the nucleus, or get incorporated to the genome. A basic course of biology would be enough to understand this "explanation" makes absolutely no sense.

This guy is a wolf in sheep's clothing. His foundation cannot be trusted for the good of humanity. He is a tech guy NOT a doctor.

This criticism would be appropriate if he was saying to trust HIM about scientific data, but he is not, he leaves the science stuff to the scientists and only deal with the funding.

There has indeed been some concern that Molnupiravir could, in the same way it disturbs the virus' RNA replication, also disturb the host's DNA replication. This is currently being examined, and I'm certain it's in focus of the clinical trials.

If you notice in my answer I never denied that a drug still being investigated may possibly be related to problems, my criticism is the completely illogical guess that makes no sense because it requires impossible things to happen commonly enough to cause problems. This is like saying that smoking is bad for your lungs because the smoke call cancer cells from people close by and makes those cells live in the smoker's lung (the first part can be true, the explanation how is complete nonsense)

This new drug is a nucleoside analog that causes mutations in the viral replication

That is correct. What is incorrect is your conclusion that

this will likely result in an increase in the appearance of variants

This is exactly what it doesn't do, it has shown to not cause viral-resistance mutations. It targets and inhibits the RNA polymerase, causing lethal mutagenesis.

Yes, the goal is to cause lethal mutations. But it will not cause lethal mutations in 100% of a patient's trillions of viruses. Plenty will survive, having undergone nonlethal mutations.

It also is not the first treatment to do this. You might know the first one, it's called "Remdesivir."

Yeah, I often complained how an immunocompromised patient was given several Remdesivir treatments each time followed by convalescent plasma, as if they were intentionally trying to create new immune escape variants.

Some have also expressed concerns, supported by animal studies, that this mutagen may increase mutations in the host (the patient). I'm guessing that this would be from conversion of the nucleoside to the corresponding deoxynucleoside, which would cause mutations when introduced into the host's DNA.

Fortunately your "guess" is based on complete ignorance of nucleotide based biology, the patients cells do not convert RNA to DNA, nor any cytoplasmic DNA has a way to go into the nucleus, or get incorporated to the genome. A basic course of biology would be enough to understand this "explanation" makes absolutely no sense.

I understand it well, I've been teaching molecular biology for many years. If you understood basic nucleotide biology you would have noticed that I never said anything about RNA being converted to DNA, or DNA moving from the cytoplasm to the nucleus. Compounds inside the cell are always being converted, broken down, and enter various pathways. I am simply suggesting that as the unnatural nucleoside is being metabolized, it might entire the pathway leading to the synthesis of the corresponding deoxynucleoside, followed by the corresponding deoxynucleotide, and finally incorporation into the DNA.

That "theory" has no scientific value, because nucleoside analogs are not necessary for RNA viruses to be constantly mutating nor the mutations are in any way more likely to result in better adaptation but the opposite.

Yes, I know the virus naturally undergoes mutations. But the compound's mode of action is through causing mutations. How can you seriously suggest it will not increase the mutation rate?!!!!

Yes, the goal is to cause lethal mutations. But it will not cause lethal mutations in 100% of a patient's trillions of viruses. Plenty will survive, having undergone nonlethal mutations.

The same as in untreated patients, except that in a lower amount, which decreases the fitness of the viruses and therefore letting the patient defeat the infection without ever selecting any of the surviving mutants, which is why variants have never been related to treatment with any nucleotide analogs.

Yeah, I often complained how an immunocompromised patient was given several Remdesivir treatments each time followed by convalescent plasma, as if they were intentionally trying to create new immune escape variants.

The problem with that complain is that it is based on fantasy scenarios, immunocompromised patients are the ones related to the appearance of viruses, and an environment of low immunicity (as for example with low vaccination rates) is the one that select and expands the dangerous variants. Immune problems have been related to the appearance of variants, completely independently of any treatment being used, and on the other hand none of the treatments you like to imagine as dangerous have been correlated with variants, which means the risk is only associated with low vaccination and patients with long infections, not with the treatments.

I understand it well, I've been teaching molecular biology for many years.

Anonymous appeals to authority are irrelevant, it is very easy to say one is anything, but without proof this is less than hearsay.

If you understood basic nucleotide biology you would have noticed that I never said anything about RNA being converted to DNA, or DNA moving from the cytoplasm to the nucleus.

That would be an even less likely scenario than the one already described, because it completely depends not only on the pool of dNTPs to be scarce enough to make nucleotides a necessary source, but also that molnupiravir to be recognized by the ribonucleotide reductase in any detectable way compared with the hugely more common natural available sources for DNA replication, there is about zero evidence of this happening. And this would be terribly easy to observe in the lab because it can be readily tested in cells, not even needing animal experiments to be detected. Its activity as an antiviral of course depends on its preferential use by the viral enzymes which has been proved scientifically above any rational doubt.

Yes, I know the virus naturally undergoes mutations. But the compound's mode of action is through causing mutations. How can you seriously suggest it will not increase the mutation rate?!!!!

Try to read the whole answer, nucleoside analogs promote mutations above what the virus can recover, meaning that all mutants produced are less fit than the ones produced during normal viral replication, this means progeny is selected against by the immune system because of low numbers being produced.

This is a well studied process and the scientific consensus at the moment is clear, the mutation rate promoted by antivirals is lethal to the virus and do not promote the appearance of better fit variants, this is as easy to prove as simply looking at the official communications from the best institutes of science, hospitals and universities, none of which mention your imaginary theory as having any merit.

It is terribly difficult to believe the best minds in the whole world are all wrong, and a nameless person in the internet is right.

And this would be terribly easy to observe in the lab because it can be readily tested in cells, not even needing animal experiments to be detected.

Yes, and it has been shown to be mutagenic in animal cells:

β-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells

https://pubmed.ncbi.nlm.nih.gov/33961695/

"However, NHC also displays host mutational activity in an animal cell culture assay, consistent with RNA and DNA precursors sharing a common intermediate of a ribonucleoside diphosphate. These results indicate highly active mutagenic ribonucleosides may hold risk for the host."

Yes, and it has been shown to be mutagenic in animal cells:

And again, the mutational risk is one I have already mentioned, but your proposed mechanism could only work in deeply non-physiological situations that are only possible on cells and not in actual use in humans, this is once again your complete misrepresentation of studies as if they were how a medical intervention is used on actual patients, which would make it valid also to say that non-vaccinated people have a 100% risk of dying of COVID (which also only apply to experimental situations).

This can be said about almost absolutely everything, including ivermectin for example

https://pubmed.ncbi.nlm.nih.gov/19056171/

Does this prove to you that ivermectin is mutagenic (even at similar doses as molnupiravir)? because if not, that would be having double standards.

It is also interesting how you were unable to get any reference at all from a respected institution of medicine or science supporting your mistaken theory that antivirals promote the appearance of variants, this should be clear enough for anybody to understand that it has no actual scientific value, specially how actual data prove no treatment has been ever correlated with the appearance of variants.