6 ms·

I enjoyed this article explaining in more detail how the drug works, though much of it goes over my head: https://www.nature.com/articles/s41594-021-00657-8 htt

I enjoyed this article explaining in more detail how the drug works, though much of it goes over my head: https://www.nature.com/articles/s41594-021-00657-8 https://www.nature.com/articles/s41594-021-00657-8 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.

SamBam 5y ago
> 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.
- DominikPeters 5y ago
  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.
  - AndrewBissell 5y ago
    It's also known to be mutagenic in mammalian cells, see the link I posted in a reply to the parent.
- rossdavidh 5y ago
  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.
AndrewBissell 5y ago
Seems like a lot of added potential risk for anyone at low odds of being hospitalized for Covid. https://pesquisa.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/pt/covidwho-1250916 https://pesquisa.bvsalud.org/global-literature-on-novel-coro...
- roflc0ptic 5y ago
  Curious why this is downvoted. Is this person wrong? It seems like an important detail if the drug is actually mutagenic in mammalian cells.
  - sterlind 5y ago
    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.) See my reply to them for more details.
    - cinntaile 5y ago
      Judging from his comment history he seems to spread a lot of this kind of covid "doubting" information.
- cinntaile 5y ago
  It clearly states that clinical use should be carefully considered, so don't worry they're aware of its side-effects.
- sterlind 5y ago
  Full text here it's not trivial to find [1]. 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. 1. https://academic.oup.com/jid/article/224/3/415/6272009?login=true https://academic.oup.com/jid/article/224/3/415/6272009?login... 2. https://academic.oup.com/view-large/figure/283696469/jiab247f0001.jpg https://academic.oup.com/view-large/figure/283696469/jiab247... 3. https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jid/224/3/10.1093_infdis_jiab247/1/jiab247_suppl_supplementary_figure_s4.jpeg?Expires=1636120100&Signature=46F7l7qKHHhve-m6e~E39-3Fqhs9Jd8rXk-Y4pKsa8raT-uKxnOGRJlQ4AD-TUpM2TtSBL2ygq-EpTpaxPWnxEk69Bw4LgT4ZnlJE1SetT2vC2lEIjp1horcdstiBAqw8T9cAfvU8v0c~4l89gHURdVl0eKAqJlWoqH547GXNPwDHEsSvcMe4yUR060e9QT6vcYz7gintGnI0hDGpRrSYyXFiUg2-xMfSCxlv~F3b10yJBWX1UrsPt6ZC-BJ2EMaPLpdPfWrhQzy4TQSw9TSJxq6niS2h7eexV4qX3vUIFg6AyN5zBb-sDGmT9NwZb-e6bxzPfcuCC-xUa9BHrya2w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA https://oup.silverchair-cdn.com/oup/backfile/Content_public/...
jonnycomputer 5y ago
The wikipedia article on the drug mentions worry about it being a mutagen with some kind of controversy. Difficult for this layman to evaluate.

SamBam 5y ago

> 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.

DominikPeters 5y ago
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.
- AndrewBissell 5y ago
  It's also known to be mutagenic in mammalian cells, see the link I posted in a reply to the parent.
rossdavidh 5y ago
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.

AndrewBissell 5y ago

Seems like a lot of added potential risk for anyone at low odds of being hospitalized for Covid. https://pesquisa.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/pt/covidwho-1250916 https://pesquisa.bvsalud.org/global-literature-on-novel-coro...

roflc0ptic 5y ago
Curious why this is downvoted. Is this person wrong? It seems like an important detail if the drug is actually mutagenic in mammalian cells.
- sterlind 5y ago
  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.) See my reply to them for more details.
  - cinntaile 5y ago
    Judging from his comment history he seems to spread a lot of this kind of covid "doubting" information.
cinntaile 5y ago
It clearly states that clinical use should be carefully considered, so don't worry they're aware of its side-effects.
sterlind 5y ago
Full text here it's not trivial to find [1]. 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. 1. https://academic.oup.com/jid/article/224/3/415/6272009?login=true https://academic.oup.com/jid/article/224/3/415/6272009?login... 2. https://academic.oup.com/view-large/figure/283696469/jiab247f0001.jpg https://academic.oup.com/view-large/figure/283696469/jiab247... 3. https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jid/224/3/10.1093_infdis_jiab247/1/jiab247_suppl_supplementary_figure_s4.jpeg?Expires=1636120100&Signature=46F7l7qKHHhve-m6e~E39-3Fqhs9Jd8rXk-Y4pKsa8raT-uKxnOGRJlQ4AD-TUpM2TtSBL2ygq-EpTpaxPWnxEk69Bw4LgT4ZnlJE1SetT2vC2lEIjp1horcdstiBAqw8T9cAfvU8v0c~4l89gHURdVl0eKAqJlWoqH547GXNPwDHEsSvcMe4yUR060e9QT6vcYz7gintGnI0hDGpRrSYyXFiUg2-xMfSCxlv~F3b10yJBWX1UrsPt6ZC-BJ2EMaPLpdPfWrhQzy4TQSw9TSJxq6niS2h7eexV4qX3vUIFg6AyN5zBb-sDGmT9NwZb-e6bxzPfcuCC-xUa9BHrya2w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA https://oup.silverchair-cdn.com/oup/backfile/Content_public/...

jonnycomputer 5y ago

The wikipedia article on the drug mentions worry about it being a mutagen with some kind of controversy. Difficult for this layman to evaluate.