This is not my field. But if there is a pill that can reduce death by 50% from the virus, I would like to know more about it.
> Bright's concerns that similar drugs in its class have mutagenic properties
As a layperson, this instantly raises a red flag in my mind. Should I be concerned? Why, or why not? More importantly, where can I find research that elucidates this for me?
>That's the effect of NHC and of molnupiravir. What about the bad side? Well, auxh nucleosides can also be taken up by many other enzymes, including those that handle our own nucleic acids, so some of them are mutagenic. Indeed, that's how NHC was first characterized, as a mutagen in bacteria. They also tend to be cytotoxic, via a number of mechanisms, and nucleoside drug candidates are notorious for wiping out in human trials due to toxicity in the liver, kidneys, and other organs. That was a feature of the 2012 scramble in the hepatitis C area, where Bristol-Myers Squibb paid 2.5 billion for a nucleoside addition to its proposed therapeutic cocktail, only to see it all demolished within a few months when it turned out to have severe problems in human trials. From this story and others you can also conclude that you don't necessarily get a good reading on this stuff in animal trials - another feature of Fun With Nucleosides.[0](Derek Lowe)
There are quite a few nucleoside analogues that have been used for HIV treatment: AZT, Zerit, FTC, Videx, Abacavir, 3TC, Hivid. There may be others I'm missing.
Of these, only Abacavir and FTC (as part of Truvada) are still used, the others have fallen out of use or are no longer even manufactured due to their bad side effect profiles and propensity for severe adverse reactions. 'Nuke-sparing' regimen planning specifically would combine other classes of drugs to avoid this class due to side effect issues.
I think it's great to have this new treatment option but this class of medications is well known for its side effects. Avoiding vaccines as 'unproven' and then going for this in particular I would consider eye rollingly wrong headed.
I'm not sure if this is tightly related, but here is Bright's whistleblower complaint [1] because it seems that mutagenic concerns are a different issue?
> During the meeting, Dr. Painter and Mr. Clerici presented a drug, EIDD-2801, as a “cure all” for influenza, Ebola, and nearly every other virus.
> They requested that BARDA urgently invest millions of dollars into their “miracle cure.” Emory’s presentation included limited data, and no data at all from human trials. Dr. Bright asked targeted questions to understand the science behind the drug and its potential to safely treat patients. Dr.
Bright knew that similar experimental drugs in this class had been shown to cause reproductive toxicity in animals, and offspring from treated animals had been born without teeth and without parts of their skulls. Dr. Bright accordingly asked Dr. Painter and Mr. Clerici about clinical trials, including whether Emory had conducted a reproductive study for toxicity, which they had not.
Molnupiravir, being a polymerase inhibitor (in layman's terms it "jams up replication machinery"), has the potential for mutagenicity. In fact it was dropped by a Gilead subsidiary for this exact reason. [1]
> A company called Pharmasset Inc. (a hepatitis C drugmaker Gilead bought in 2011) investigated molnupiravir’s main ingredient around the turn of the century, but it abandoned development over concerns that it was mutagenic, meaning it could lead to birth defects.
Actually the article is slightly wrong, mutagenic is causing mutations in the host's germ or somatic DNA, teratogenic is causing birth defects. Most mutagens are teratogens too. From the Dr Bright complaint filing, Bright was concerned about reproductive toxicity (teratogenicity) so I'm not sure if the article meant to say teratogenic, or the concern is that the drug is both mutagenic and teratogenic (polymerase drugs tend to be both).
Subsequent tests seem to have shown a lack of mutagenic activity in hosts (eg Painter 2021), at least enough to get through safety trials, which is excellent. But looking at it from a structural activity point of view, molnupiravir is way, way more likely to have a DNA-affecting mechanism than mRNA. It has also shown mutagenic effect in vitro [2]. Nonetheless, a small increase in cancer risk years down the road (especially in the over-70 crowd) is likely worth the 50% (!) reduction in mortality.
It's probably fine, as long as you aren't pregnant. Like all drugs, it's about risk/benefit ratio. The covid vaccine has a much more favorable profile and should still be the preferred option. I doubt it'll be approved for pregnant women without a reproductive toxicity study.
> Bright's concerns that similar drugs in its class have mutagenic properties
As a layperson, this instantly raises a red flag in my mind. Should I be concerned? Why, or why not? More importantly, where can I find research that elucidates this for me?