9 ms·
The Achilles Heel of the Coronavirus
- CyanLite4 5y agoA bit redundant. We know how to “kill” the SARS-CoV-2 virus in vitro (in a test tube). Ammonia, bleach, UV light. Heck, even diluted mouthwash will do the trick. The problem is that none of these approaches are safe in vivo (in the body). All of the approaches the article talks will require years of human testing. The drug EIDD-2801 does similar things but has yet to pass testing even after 12 months of studies.
- stonogo 5y agoThis isn't about "killing" the virus, it's about inhibiting its ability to reproduce. Pointedly, it's about doing so without introducing mutagens like EIDD-2801, but instead by inhibiting a specific ribosomal behavior induced by a component of the virus. Finding a safe mechanism to do so is the next step in their research. I suspect your interpretation of the article might be off. This work is a great example of the new insights we get from recent advances in cryo-electron microscopy. It's much easier to formulate responses to mechanisms when we can get clear pictures of the sites in question.
- failwhaleshark 5y agoSuppose protein folding simulation and manufacturing can rapidly advance well beyond current levels. It seems like a hypothetical synthetic immune system that whitelists every configuration of every protein an individual can possibly generate and excludes everything else (if possible) would be a way to blanket eliminate unknown unknowns proactively like SELinux for the body.
- pontifier 5y agoI did a thought experiment about how the immune system must work and came up with a simple system using only mechanisms that I know are available molecularly. If you could have a bunch of random protein sensors that undergo a training phase where they learn what "Host" is. Anything that makes a "detection" during training is discarded. Anything that doesn't is either never going to detect stuff, or might detect something "Foreign". These then float around your blood stream and either do nothing until they are lost, or go crazy replicating and raising the alarm when something Foreign shows up. A danger with this method is random sequences that are just really bad at detecting "Host" or a training period that is cut short. This might lead to autoimmune responses. This thought might give some hints about how to combat autoimmune diseases without disrupting the greater immune system.
- failwhaleshark 5y agoPerhaps an improved auto-recognition "self" system that uses something like public key crypto and a challenge-response.
- pontifier 5y agoThe biggest advantage we have is that we might identify the responsible bad signaler, and then target it for removal somehow. I wouldn't want to mess with it more than that...for now.
- deleted 5y ago[deleted]
- hermitdev 5y agoSuch a system would effectively halt evolution, though.
- adrianN 5y agoI don't think biological evolution is an important factor in modern humans.
- thesnide 5y agoThat comment is spectaculary equally insightful, humorous and sad.
- bbarnett 5y agoWithin 20 years every newborn will be gene edited. Likely, human intelligence and world view will end up being derived from a handful of genes, thus further blinding humanity to data outside of our worldview. Imagine a world where everyone has the same level, and type, of emotional response to data, feels the same as a result of environmental stimuli, eg cold/warm/wet etc. Imagine a world where if your next door neighbor cannot figure out something, no one ever can, for there are no geniuses or dullards. The sameness of thought will make future society dull, compared to the Amish. (Think it won't happen that fast? Laws will prevent it? Imagine your neighbour flies off-shore, and comes back with his child gene edited for appearance, intelligence, health. Now you are about to have a child. What do you do? Compared to the neighbour's child, yours will be dull, sickly, ugly. What will you do? Now imagine the rich and powerful do this, bit you cannot afford it? 1%er indeed.)
- londons_explore 5y agoYou should read Brave New World by Aldous Huxley.
- adrianN 5y agoI think you overestimate the importance of genes. Twins are not identical people.
- emmelaich 5y agoThis trial says UV light can be safe. Take it for what you will. https://www.medrxiv.org/content/10.1101/2021.03.05.21252997v1.full.pdf https://www.medrxiv.org/content/10.1101/2021.03.05.21252997v...
- xx789 5y agoI believe Trump is famous for discovering this and they were going to try how drinking or injecting bleach could be used?
- bawolff 5y agoThe article's about a method they hope will be safe in the body. Maybe they're right maybe they are wrong, but hardly seems redundant.
- thepangolino 5y agoWe also have known about this for a long while. A pity the article doesn't mention what the "compounds" are zinc based and are the mechanism of action of HCQ based treatments.
- williesleg 5y agoTrump said UV light, the fucker was right all the time.
- whall6 5y agoPretty interesting how well the article explains such a complex concept.
- gmuslera 5y agoFor 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.
- DennisP 5y agoI wouldn't want to do it permanently but doing it temporarily, to treat a severe acute infection, seems like a pretty good tradeoff. Especially after you've done your clinical safety trials to be sure.
- bawolff 5y agoDoing it just long enough in people with a severe infection so they don't die of the infection seems like a reasonable trade off. Nobody's suggesting we use this as a daily supplement in healthy people.
- IAmGraydon 5y agoThe article doesn’t say it’s “rarely used”. It says it “rarely happens”. It is not supposed to happen: > Frameshifting almost never happens in our cells. It would lead to dysfunctional cellular proteins. So the drug would disable an aberrant behavior that coronaviruses depend upon to replicate. This doesn’t sound like a bad thing. It’s also why trials exist.
- ampdepolymerase 5y ago"Dysfunctional proteins" is a vast understatement. Too much frameshifting leads to cancer.
- aaron_m04 5y agoI don't see how it could lead to cancer. We are talking about a translation error, not a replication error.
- koeng 5y agoI'd say the achilles heel is most likely in the genomic structure, which unlike influenza, is less likely to recombine.
- Clostridium 5y agoNot true, the genome of viruses is very variable/evolvable due to its high mutation rates.
- koeng 5y agoI 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. So, yes, true.
- tryonenow 5y ago>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.
- monkeycantype 5y agohttps://en.wikipedia.org/wiki/Viral_evolution#:~:text=Bubble%20theory https://en.wikipedia.org/wiki/Viral_evolution#:~:text=Bubble... you might find this interesting. bubble theory imagines that interacting molecules, let's call them 'scripts', formed simple self replicating metabolisms inside the cavities of hydrothermal vents. At a script level there are two successful strategies: participate in a co-operative network or exploit a co-operative network to self replicate you. At a community level, excluding non-contributors is beneficial and this pre dates and perhaps leads to the development of cell membrane. In this view cells and viruses co-evolve from the same origin by pursuing different strategies. It's game theory and tragedy of the commons from day one. Piast, Radosław W. ‘Shannon’s Information, Bernal’s Biopoiesis and Bernoulli Distribution as Pillars for Building a Definition of Life’. Journal of Theoretical Biology 470 (7 June 2019): 101–7. https://doi.org/10.1016/j.jtbi.2019.03.009 https://doi.org/10.1016/j.jtbi.2019.03.009. https://www.sciencedirect.com/science/article/pii/S0022519319301109 https://www.sciencedirect.com/science/article/pii/S002251931...
- tryonenow 5y agoEmergence is fascinating. Life is arguably the most striking example in the known universe. In this case I'm sure the messy nature of exploitation accelerated (or even enabled) evolution of more complex structures. Consider it a primitive archetype for an abusive but also ultimately symbiotic relationship.
- webwielder2 5y agoNot very sporting to target your own exploits.
- dnautics 5y agoif we targeted this, would the coronavirus simply be able to figure out a way to regulate its proteins some other way?
- pygy_ 5y agoThere’s only one way to know for sure...
- StavrosK 5y agoIf we got rid of all living organisms entirely, it stands to reason that the virus wouldn't be able to go on living by itself. Therefore, between the current situation and now, there's a point where it's too hard for the virus to keep existing in its current form. There's no reason to suspect that the virus will be able to tackle anything we throw at it without just dying out. It might not be the vaccine, but it'll be something (assuming it doesn't just turn into a common cold eventually and we lose interest.
- f6v 5y agoFrameshifting might play a role in healthy gene regulation https://doi.org/10.1002/bies.201500131 https://doi.org/10.1002/bies.201500131
- yborg 5y agoRemarkable work, I wasn't aware that it was possible to image transcription at the ribosome like that.
- wiz21c 5y agoYep, I've already seen that kind of animations. That's super cool !
- FriedrichN 5y agoAnyone else getting SSL_ERROR_UNSAFE_NEGOTIATION?
- londons_explore 5y agojust means it's an old server.
- bawolff 5y agoIts not using the new secure renegotiation. So its possibly vulnerable to https://blog.ivanristic.com/2009/11/ssl-and-tls-authentication-gap-vulnerability-discovered.html https://blog.ivanristic.com/2009/11/ssl-and-tls-authenticati... but more likely they have renegotiation disabled entirely.
- FartyMcFarter 5y agoDoes 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 https://en.wikipedia.org/wiki/Ribosomal_frameshift#Function
- rsa4046 5y ago“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! :)
- folli 5y agoCorrect, 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.
- platz 5y ago> 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' happen.
- anoncake 5y ago> Not confidence inspiring that their drugs are doing things that they don't fully understand. That's really common.
- cainxinth 5y agoSo common it would blow the average patient’s mind. The mechanism of action for Tylenol is still not entirely understood.
- platz 5y agoSo 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.
- anoncake 5y agoWe 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.
- platz 5y agoWow, you still think it's going to be eradicated