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The Achilles Heel of the Coronavirus

ethz.ch

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Re: The Achilles Heel of the Coronavirus

#71

Post by cainxinth »

anoncake wrote: post #70
platz wrote: post #66

> one of the two reduced viral replication by inhibiting ribosomal frameshifting, while the other might act through a different mechanism. Just another random different mechanism there. Wonder what it 'might' be doing. Probably wasn't important. Not confidence inspiring that their drugs are doing things that they don't fully understand. I'm sure we can put this in humans without any adverse effects that 'might' happe…

> Not confidence inspiring that their drugs are doing things that they don't fully understand. That's really common.

So common it would blow the average patient’s mind. The mechanism of action for Tylenol is still not entirely understood.

Re: The Achilles Heel of the Coronavirus

#72

Post by ruinthemagic »

anoncake wrote: post #70
platz wrote: post #66

> one of the two reduced viral replication by inhibiting ribosomal frameshifting, while the other might act through a different mechanism. Just another random different mechanism there. Wonder what it 'might' be doing. Probably wasn't important. Not confidence inspiring that their drugs are doing things that they don't fully understand. I'm sure we can put this in humans without any adverse effects that 'might' happe…

> Not confidence inspiring that their drugs are doing things that they don't fully understand. That's really common.

Yup. From hazy chemistry degree knowledge, we don't know how most drugs actually work. Designing drugs based on the shapes or proteins etc is pretty cutting edge stuff.

And also the nature of organic chemistry is that even if a drug does work a certain way, it probably has several other pathways it can go down. That is, only a certain (probably low) percentage of the drug will actually have the effect you want, the rest will take part in other reactions.

Re: The Achilles Heel of the Coronavirus

#73

Post by platz »

cainxinth wrote: post #71
anoncake wrote: post #70

Earlier quoted context omitted.

> Not confidence inspiring that their drugs are doing things that they don't fully understand. That's really common.

So common it would blow the average patient’s mind. The mechanism of action for Tylenol is still not entirely understood.

So the idea based on other threads is to eradicate covid with this method.

I can't wait to see how the public would react to this tech, given the response to mRNA vaccines, trying to blow their minds on this one.

Re: The Achilles Heel of the Coronavirus

#74

Post by anoncake »

platz wrote: post #73
cainxinth wrote: post #71

Earlier quoted context omitted.

So common it would blow the average patient’s mind. The mechanism of action for Tylenol is still not entirely understood.

So the idea based on other threads is to eradicate covid with this method. I can't wait to see how the public would react to this tech, given the response to mRNA vaccines, trying to blow their minds on this one.

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.

Re: The Achilles Heel of the Coronavirus

#75

Post by rsa4046 »

FartyMcFarter wrote: post #52

Does anyone have a sense of why the virus evolved to use this strange "frameshift" mechanism? Is this "hack" somehow advantageous enough for the virus that it would evolve it, rather than using more standard mechanisms? edit - oh, wikipedia claims this is a compression mechanism, that's amazing! https://en.wikipedia.org/wiki/Ribosomal_frameshift#Function

“In the case of a translating ribosome, a frameshift can either result in nonsense (a premature stop codon) after the frameshift, or the creation of a completely new protein after the frameshift. In the case where a frameshift results in nonsense, the NMD (nonsense-mediated mRNA decay) pathway may destroy the mRNA transcript, so frameshifting would serve as a method of regulating the expression level of the associated gene.”

Nonsense-mediated mRNA decay. Love this term! :)

Re: The Achilles Heel of the Coronavirus

#76

Post by folli »

FartyMcFarter wrote: post #52

Does anyone have a sense of why the virus evolved to use this strange "frameshift" mechanism? Is this "hack" somehow advantageous enough for the virus that it would evolve it, rather than using more standard mechanisms? edit - oh, wikipedia claims this is a compression mechanism, that's amazing! https://en.wikipedia.org/wiki/Ribosomal_frameshift#Function

Correct, you can encode two different proteins with the amount (length) of DNA usually used for one protein. This is not really relevant for higher life forms, as DNA is cheap. But for a virus this 'cost saving' can really matter when trying to replicate quickly and cheaply.

Re: The Achilles Heel of the Coronavirus

#77

Post by Kiro »

Clostridium wrote: post #58
roenxi wrote: post #56

Earlier quoted context omitted.

> 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…

Phase IV trials are only undertaken after formal approval by FDA and EDA; they are not relevant in the current context. The current vaccins (including Pfizer, moderna which clearly use a novel mechanism for delivery) also don't have phase IV data yet. Thank God they have been approved though, they are currently clearly the way out of a pandemic that so far has claimed 3.4 million deaths. I really don't understand wha…

You are allowed to raise concerns without being labeled an antivaxxer.

Re: The Achilles Heel of the Coronavirus

#78

Post by ben_w »

542354234235 wrote: post #69
roenxi wrote: post #56

Earlier quoted context omitted.

> 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…

> But it is, nevertheless, risky. But this assumes there is no risk to not doing it, which is false. Getting sick, suffering long term damage to your body, or dying are all very real risks of covid-19 that we already know about. We also have no idea what all the long term less evident negative effects are from covid-19. We have no idea if an asymptomatic covid infection does some sort of long term damage. So we are w…

There’s also the second-order problem of normal people generally being bad at statistics[0], and therefore a significant number (even when a minority) assuming that any report that “one specific vaccine turns out to be harmful” implies “the general concept of vaccination is bad”.

We need people to be confident in the long-term, as well as to have a solution quickly in the short-term.

[0] hence, for example, the use of the word “obscure” in the headline “The obscure maths theorem that governs the reliability of Covid testing”: https://www.theguardian.com/world/2021/apr/18/obscure-maths-...

Re: The Achilles Heel of the Coronavirus

#79

Post by platz »

anoncake wrote: post #74
platz wrote: post #73

Earlier quoted context omitted.

So the idea based on other threads is to eradicate covid with this method. I can't wait to see how the public would react to this tech, given the response to mRNA vaccines, trying to blow their minds on this one.

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.

Wow, you still think it's going to be eradicated

Re: The Achilles Heel of the Coronavirus

#80

Post by Robotbeat »

ben_w wrote: post #78
542354234235 wrote: post #69

Earlier quoted context omitted.

> But it is, nevertheless, risky. But this assumes there is no risk to not doing it, which is false. Getting sick, suffering long term damage to your body, or dying are all very real risks of covid-19 that we already know about. We also have no idea what all the long term less evident negative effects are from covid-19. We have no idea if an asymptomatic covid infection does some sort of long term damage. So we are w…

There’s also the second-order problem of normal people generally being bad at statistics[0], and therefore a significant number (even when a minority) assuming that any report that “one specific vaccine turns out to be harmful” implies “the general concept of vaccination is bad”. We need people to be confident in the long-term, as well as to have a solution quickly in the short-term. [0] hence, for example, the use o…

But I’m not sure the hyper risk averseness actually helps normal people to have a more realistic perspective on statistical risk. When people see a drug or vaccine that’s put on pause out of an abundance of caution, they don’t think, “oh, look how careful they’re being! I think I’ll trust their process more.” They think, “Wow, look how inconsistent and unreliable this is! I don’t know if I can trust the FDA or vaccines at all!”

So I’m skeptical of folks using 2nd order arguments about why going beyond rational approaches to risk is a good idea. People see overly risk-averse behavior by the FDA as evidence that the risk is actually high (relative to other stuff in their lives).

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