Briefly, it causes the copying process of viral RNA to go wrong by increasing the number of G-to-A and C-to-U mutations. A potential worry is that such mutations will also increase in places where we don't want them, such as in host DNA, but apparently at least for mitochondrial RNA things look good.
> A potential worry is that such mutations will also increase in places where we don't want them
Can anyone speak to how the drug avoids this? I've tried reading the literature, such as the Nature link above, and have failed to see what makes the drug specific to the virus.
Nature link says the drug targets RdRp specifically which is a type of RNA copying mechanism (mostly?) confined to viruses. Wikipedia says about RdRp:
> RdRps can be used as drug targets for viral pathogens as their function is not necessary for eukaryotic survival. By inhibiting RNA-dependent RNA polymerase function, new RNAs cannot be replicated from an RNA template strand, however, DNA-dependent RNA polymerase will remain functional.
Well one possibility is that, like chemotherapy or radiation vs. cancer, it's worth the risk. The body has DNA-repair mechanisms that could clean up the mess, if you're only taking the pill for a short time. The virus does not. Just a guess.
This study doesn't show that molnupiravir (rNHC) is genotoxic at levels effective for treating covid. Dosage of 1µm reduced COVID+ cells by 15x, while 3µm removed the infection entirely. [2] 1µm and even 3µm dosing didn't lead to any statistically significant genotoxicity, only 10µm showed effects [3].
The authors know this, because their conclusion is that the risk of genotoxicity "might not be zero." They have not demonstrated that therapeutic doses cause any statistically significant increase in mutations.
It is misleading but not directly wrong. Excessively high doses lead to mutations, but that's true for aspartame too. Nothing suggests that a therapeutic dose for a short time will give you cancer any more than X-rays from plane travel (i.e. there's a causal mechanism, but it's not statistically significant.)
Briefly, it causes the copying process of viral RNA to go wrong by increasing the number of G-to-A and C-to-U mutations. A potential worry is that such mutations will also increase in places where we don't want them, such as in host DNA, but apparently at least for mitochondrial RNA things look good.