For me sounds scary to disable a mechanism in all our cells that is "rarely used". Negative knowledge covers what we don't know and what we don't know that we don't know, and that rarely could be less rare than we thought, doing maybe not do frequent but anyway essential things, for all or some cells.
This is not actually a mechanism in our cells. The virus RNA folds in a particular way that interferes with how the ribosome usually works. Imagine it like a machine that takes in a an RNA strand, and you make a knot in the strand. The machine can untangle the knot with some force, but slips while it is doing this and the alignment of the strand shifts and the machine continues on a different position on the strand t…
I'd say the achilles heel is most likely in the genomic structure, which unlike influenza, is less likely to recombine.
Not true, the genome of viruses is very variable/evolvable due to its high mutation rates.
I wasn’t talking about mutation rates. Influenza has mini-chromosomes which it can swap between strains, leading to more variants since they can swap those mini-chromosomes. SARS-CoV-2 has a single linear genome - only recombination on the RNA level or accumulation of mutation will allow for evolvability. Also, viruses massively differ in their own mutation rates.
We can't eradicate Covid by making all the birds wear masks, we can't eradicate it by vaccinating all the birds, and we certainly can't eradicate it by asking all the birds to go to the doctor to get treated when they get Covid.
Au contraire, this is exactly the thing that we should look into in an emergency! RNA-slippage is a well-known mechanism that a healthy cell has safeguards against. The corona virus exploits this slippage, so disabling it using a drug is a novel and smart approach as this presents a likely very specific attack surface (meaning side-effects will likely be few). Ignoring this mechanism would be very imprudent. What mak…
> What makes you think the usual precautions (cell lines, animal models, phase I, II, III trials) will not be taken as per usual? You've skipped one of the usual phases, which is Phase IV trials. Cell lines -> Phases III trials aren't enough to catch long term side effects, because they are all done quickly. An experimental mechanism passing Phase III trials is insufficient to prove it is safe. It proves that any neg…
Sigh. Phase IV trials are not part of the approval process; they follow formal FDA or EDA approval and noone is doubting they are important. Regarding risky: it is a well managed risk, and one that you simply cannot not take in the face of a debilitating condition, let alone a deadly pandemic. How do you propose new drugs can ever be introduced at all? And again: the Moderna and Pfizer (and also Janssen, somewhat) vaccines use a novel method of delivery, have been mass-rolled out. You seem to be saying that this should never have been done.
Au contraire, this is exactly the thing that we should look into in an emergency! RNA-slippage is a well-known mechanism that a healthy cell has safeguards against. The corona virus exploits this slippage, so disabling it using a drug is a novel and smart approach as this presents a likely very specific attack surface (meaning side-effects will likely be few). Ignoring this mechanism would be very imprudent. What mak…
> What makes you think the usual precautions (cell lines, animal models, phase I, II, III trials) will not be taken as per usual? You've skipped one of the usual phases, which is Phase IV trials. Cell lines -> Phases III trials aren't enough to catch long term side effects, because they are all done quickly. An experimental mechanism passing Phase III trials is insufficient to prove it is safe. It proves that any neg…
You can't prove safety.
You can demonstrate a high degree of safety.
But demands to prove it can always ask for more more more.
it could, in theory lead to cancer, but you'd have to be super unlucky. (frameshift -> accidentally leads to some sort of oncogene agonist)
Even then, frame shifts are one off events, so you’d end up with a single instance of an oncogene that would quickly get recycled.
exactly. Don't know about quickly. Half lives of single proteins can be highly variable. You can have a single protein live long enough to destroy an entire cell (ricin); it evades degradation by not having many lysines and never being ubiquitinated.
>Frameshifting almost never happens in our cells. It would lead to dysfunctional cellular proteins; however, certain viruses, such as coronaviruses and HIV, depend on a frameshifting event to regulate levels of viral proteins. For example, SARS- CoV-2 - the virus that causes COVID- 19 - is critically dependent on frameshifting promoted by an unusual and intricate fold in the viral RNA. God is a hacker.
Your reply got flagged, I’m curious whether that was auto or human. I was talking with my daughter last night about ambiguity in speech and interpretation last night, and about the space of true things well intentioned people avoid, because bad faith actors with an unspoken partisan agenda use that space as area of tenuous ambiguity into which they implausibly retreat when challenged on the hideous ideas they are trying to ship.
I read your comment as a reflection in the hideous cruelty of life, anyone studying biology or medicine beyond high school confronts the cold indifferent ugliness of nature, and the enormity and absurdity of the task we have to build a kind compassionate society on this substrate. But once you factor in ambiguity, your comment keyword matches the crypto-misogyny leading comments of trolls claiming to know something about social Darwinism.
Perhaps others read your comment in that light.
On the whole I enjoy how this site is moderated, I think it’s close to optimum, but general optimization means specifics are sacrificed, and this is one where I would like to have participated in a quite backstage conversation to understand the perspective of the participants
>Frameshifting almost never happens in our cells. It would lead to dysfunctional cellular proteins; however, certain viruses, such as coronaviruses and HIV, depend on a frameshifting event to regulate levels of viral proteins. For example, SARS- CoV-2 - the virus that causes COVID- 19 - is critically dependent on frameshifting promoted by an unusual and intricate fold in the viral RNA. God is a hacker.
Your reply got flagged, I’m curious whether that was auto or human. I was talking with my daughter last night about ambiguity in speech and interpretation last night, and about the space of true things well intentioned people avoid, because bad faith actors with an unspoken partisan agenda use that space as area of tenuous ambiguity into which they implausibly retreat when challenged on the hideous ideas they are try…
I'm completely surprised by the negative reaction to my comment. I think people are misinterpreting my use of the word hacker, and I don't even mean to imply that God exists - only that the universe is intricately clever and whether by intent or by emergence this frameshift exploit on which some viruses rely for reproduction is an absolutely brilliant trick. My comment was made in reverence. Or perhaps it's the implication of intelligent design that upset the downvoters/flaggers?
>I read your comment as a reflection in the hideous cruelty of life, anyone studying biology or medicine beyond high school confronts the cold indifferent ugliness of nature
Perhaps my comment came off callously then. I made no value judgement, it was only the design that I meant to describe. Nuclear weapons are terrible things, but they are still technical works of art.