A Triple Hit On Merck's Wonder Drug
It seems the wonder is that Merck thinks it can push this drug on a public that is growing more wary by the day of Covid narratives and mandates. There are three hits on Molnupiravir today:
First, from Barron’s:
As it turns out, all the scientists and doctors who insisted that Merck's "revolutionary" COVID drug molnupiravir is extremely safe weren't faithfully adhering to "the science" after all. Because according to a report published Thursday by Barron's, some scientists are worried that the drug - which purportedly cut hospitalizations in half during a study that was cut short - could cause cancer or birth defects.
I guess I’m past worrying about birth defects, but … take a chance on cancer? No thanks.
Zerohedge also takes a swipe at former head of FDA, Scott Gottlieb, for endorsing a basically untested drug, then goes on to quote Barron’s on what the problem is:
Some scientists who have studied the drug warn, however, that the method it uses to kill the virus that causes Covid-19 carries potential dangers that could limit the drug’s usefulness.
Molnupiravir works by incorporating itself into the genetic material of the virus, and then causing a huge number of mutations as the virus replicates, effectively killing it. In some lab tests, the drug has also shown the ability to integrate into the genetic material of mammalian cells, causing mutations as those cells replicate.
If that were to happen in the cells of a patient being treated with molnupiravir, it could theoretically lead to cancer or birth defects.
Next, Reuters is carrying a report from India—Indian drug authorities want to discontinue trials of Molnupiravir because they basically don’t see any point:
Merck drug less effective against moderate COVID -India regulatory source
Merck & Co's (MRK.N) experimental antiviral drug molnupiravir has not shown "significant efficacy" against moderate COVID-19, a source with the Drug Controller General of India said.
Aurobindo Pharma Ltd wants to discontinue a late-stage trial of molnupiravir in moderate COVID-19 patients, the regulator's expert committee said on Friday. read more
"There is no significant efficacy against moderate COVID and the effective efficacy is towards mild cases," the source said on condition of anonymity due to the sensitive nature of the discussions.
Finally, from a less authoritative source, but reflecting the concerns of scientists:
Most of the article is behind a paywall, but …
Merck’s Molnupiravir (also known as EIDD-2801 and MK-4482) is a mutagenic nucleotide analogue [1]. It introduces errors in the SARS-COV-2 RNA at the time of replication after proofreading, and causes lethal mutagenesis [2]. This threatens to accelerate the evolution of the coronavirus.
Any major variant of the coronavirus represents local optimum (in mutations space), maximizing coronavirus’ fitness. One- or two-point mutations cannot accomplish this. A new variant can only rise through the change of the virus-host-conditions systems, or through larger mutations set. Even a moderate increase in the point mutations frequency causes a big increase in the frequency of multi-point mutations and dangerous recombinations. Such events are too rare to be caught in small trials, but inevitable in large populations, and might lead to catastrophic consequences. The authorization and broad use of Molnupiravir is likely to breed very dangerous SARS-COV-2 variants.
Who’s in favor of a global catastrophe? Of new and “very dangerous” Covid variants? Count me out, too.
Mark, I must thank you for staying on top of the coronadoom story. You are one of two blog sites that I check daily for info that I can't find anywhere else. The breath of your reading is impressive.
Several days ago, I commented here on Molnupiravir by saying that it's just another nucleotide analog enzyme inhibitor that may or may not be toxic, depending on its' chemical and kinetic characteristics. From the stories you quote today, it appears that it's an effective anti-viral because it escapes viral proofreading, which is a key element of the chemical mechanism.
The other half of the equation is the rate of proofreading and incorporation into host DNA. Humans have both nuclear and mitochondrial polymerases. Depending on the partitioning of the drug between nuclear or mitochondrial sites, the effects may be significantly different.
Cancer would most likely result from nuclear effects if the drug escapes proofreading during human genomic replication in cells with significant genomic DNA synthesis. Mitochondrial effects would be more likely to be toxic, but not cancerous, because the entire mitochondrial genome is much smaller and turns over completely in a matter of hours and days. In other words, mutations in mitochondrial DNA would not cause cell proliferation.
I'm still hesitant to embrace the scare-mongering over cancer because I haven't seen any data, but it's certainly a plausible idea, depending, as I have said, on the chemical kinetics and specificity with human polymerases.
I just wish I wasn't retired and that I could still go behind the paywalls to read the actual science with an institutional literature account. Better yet, I wish I could get paid to write about the coronadoom science!
Currently in Lithuania
Here's a harrowing tale of what awaits:
"With no Covid Pass, my wife and I are banished from society.
We have no income.Banned from most shopping.Can barely exist.
But we will not accept authoritarianism.
Here's how life looks after one month in Lithuania,under Europe's first strict,society-wide Covid Pass regime:"
https://twitter.com/gluboco/status/1446134032027176965