6 Comments
founding
Oct 4, 2021Liked by Modern Discontent

So I have been trying to process this information over the past few days ... the Ars Technica piece (while it does a great job with the hammer synonyms) was obviously written by someone who never took a basic genetics course. This drug is basically a cytidine (one of the RNA building blocks) with a self-implosion unit attached to it. When the virus replicates it will occasionally insert this drug in lieu of a real cytidine and cause enough chaos to essentially prevent the virus from replicating its RNA genome correctly. We humans also use cytidine to transcribe our DNA into RNA so we can make proteins (enzymes are a type of protein that does things) so it is quite conceivable that this drug could ultimately interfere with our protein making (note that RNA is generally short-lived in our cells and always freshly transcribed from DNA). Also, as Zhou et al. pointed out it is conceivable that this drug can easily be converted to DNA precursors via ribonucleotide reductase. That means you now have a deoxycytidine with the self-implosion unit ready to be incorporated into your dividing cells (extra bad for female fetuses and spermatozoa). The lack of long-term affects (as is so unrefreshingly common nowadays) is unacceptable. On the surface it is a brilliant drug, but we really need to look at it from all sides. We have gotten do many things wrong in the past (lead-paint, asbestos, talcum powder, hey - let's use plastic for everything) - do we just forego safety to satisfy an immediate need (albeit for an underwhelmingly fatal virus) - prophylactic use at this point would be quite scary.

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Appreciate the well thought out response! I have been focusing on it for purely it's mutagenic effects but it would be quite interesting to think about mismatched tRNA codons that may cause the incorporation of wrong proteins. It may not create such an issue as mutagenesis but once again I would really like to see information to determine that position. Nonfunctioning proteins may trigger a cascade of events that may lead to cell death but we really need plenty more data! We always need to think about the precautionary principle and make sure that the cure is not worse than the disease.

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founding
Oct 5, 2021Liked by Modern Discontent

Yes, there are a lot of unknowns. Hopefully the drug will be metabolized quickly and removed from the body efficiently. It's not like these drugs can somehow be forced to only affect viral replication. And, Merck hasn't provided any data yet to scrutinize. But hey, it worked so great so let's just get the ball rolling with an EUA. It's also a bit hard to understand their results as presented in the press release. They say only 28 of 385 patients who received the drug were hospitalized or died (but later say none died) - so 28 were hospitalized?? Compared to 53 of 377 who received placebo (8 of them died). So there was a 95% survival rate for the entire cohort (which consists of adults with at least one known underlying medical condition that increases risk of death from COVID infection). Nothing is really known of the participants ... but they aren't allowed to be pregnant, get pregnant or get somebody pregnant (for at least 4 days after last treatment) ... which would suppose that they are aware of possible teratogenic effects ... and shouldn't you be in quarantine if you have the Rona which would not be conducive to sexual relations (just sayin...).

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The pregnancy does sound like they're entering into the realm of semantics to just cover all grounds. The measures for clinical efficacy have always been very concerning, and the idea that only acute toxicity is being looked at in the context of this drug is frustrating. It's as if the researchers are outright ignoring the mechanism of action!

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Oct 27, 2021Liked by Modern Discontent

"U.S. pharmaceutical giant Merck has agreed to share its license with a nonprofit so that its experimental covid-19 drug, molnupiravir, can be manufactured widely around the world in a deal that would expand access to the treatment in more than 100 countries."

"Last week, the Bill and Melinda Gates Foundation announced what it said was an initial investment of up to $120 million to incentivize those drugmakers to begin producing the treatment now — even before it has been approved by regulatory bodies."

https://www.msn.com/en-us/news/us/u-s-drug-company-merck-to-share-license-for-experimental-covid-19-treatment-with-nonprofit-organization/ar-AAQ0lJI?ocid=msedgdhp&pc=U531

Going worldwide.

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I would not mind if they actually did plenty of studies to really highlight it's safe. The big issue is that the carcinogenic effects of the drug would not become apparent until several years down the line. This isn't something you can somehow rush in animal studies and say it's safe.

It's just so frustrating that they haven't really covered many of the actual science.

They have money and they'll just push around whatever narrative they would like instead of trying to commit to actual science.

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