6 ms·

Inside the Coronavirus

106 points by hayderado 6y ago

hirenj 6y ago
While this might come across as a pedantic point, I don’t think CoV-2 comes in via membrane fusion, but it is rather endocytosed (i.e. the receptor is pulled back into the cell, taking the virus with it). This is an important distinction to make, because this opens the door for other opportunities to interfere in this process (e.g. stuffing around with actin dynamics). Of course, this is a pop culture depiction, but I believe that many people discount how useful such visual summaries are for even people who are deep in the field, and as such I’d hope that people spend effort sweating the details, because it does help!
- papaf 6y ago
  Could it use both methods of entry? https://www.sciencedirect.com/science/article/pii/S0166354220302060#fig3 https://www.sciencedirect.com/science/article/pii/S016635422... I cannot comment on how accurate it is, but I found the interactive overview in the Scientific American to be awesome.
  - hirenj 6y ago
    It very well could use both mechanisms, which I neglected to think about. I only think endocytosis is important because that specific mechanism uses ACE2 and heparan sulfate (which can be blocked using heparin I think).
- hirenj 6y ago
  I had no idea there was more to the page because of the weird scrolling on the site, so I missed the glycan (sugar) stuff, which is my bread and butter. I think the consensus is that there is not likely any shielding going on with the glycans (like what you would find with HIV), but there are glycans that stabilise the ACE2 binding part. Also, people have found glycans on a protein cleavage region, which I would expect could impart resistance to cleavage (a predictor I wrote from a few years back correctly predicted those sites).
  - aeternum 6y ago
    Seems like this would be much better as a video. It probably took a tons of effort to put this into a webpage and it was quite buggy and unintuitive.
acqq 6y ago
One of very interesting properties of SARS-CoV (2003) and SARS-Cov-2 (2019) is that they have their "proofreading" replication mechanisms, or in the terms of people working with computers these viruses have an "error correction device" active during the copying that allows them to have a relatively long genome which won't mutate too fast: NYT interactive April 2020, also a good visualization of some "building blocks": https://www.nytimes.com/interactive/2020/04/03/science/coronavirus-genome-bad-news-wrapped-in-protein.html https://www.nytimes.com/interactive/2020/04/03/science/coron... 2015 paper: https://www.pnas.org/content/112/30/9436 https://www.pnas.org/content/112/30/9436 2013 paper: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003760 https://journals.plos.org/plospathogens/article?id=10.1371/j... 2006 paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458802/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458802/
- pfundstein 6y ago
  Does this slow down it's ability to mutate though, potentially allowing for more effective vaccines?
  - acqq 6y ago
    Influenza viruses don't have that mechanism. That doesn't prevent humanity to have working vaccines each year for the currently important influenza viruses. The needed research was already done long ago. But regarding SARS-CoV-2, it's still too early to say anything for sure, we have lost the precious time in not learning enough from the properties of the (2003) SARS-CoV virus, not to mention western world remaining very unprepared for long after the spreading of SARS-CoV-2 started.
    - the_af 6y ago
      What about retroviruses such as HIV, where replication errors are very likely? It's almost like replication errors are a feature of HIV which makes it harder to develop a vaccine (of course, most mutations won't be helpful to the virus, but at least some will). (I'm not saying SARS-CoV-2 is the same case)
gdubs 6y ago
Around the point in the interactive where it shows how the virus swings sugar molecules around to distract the immune system I paused and marveled at the tiny universe inside our bodies. The first time I recall feeling similarly was when I first watched Cosmos as a kid, and Carl Sagan juxtaposes time lapse photography of cities against the bustling activity of cells inside the human body. We walk around every day thinking of ourselves as solid objects in a Newtonian world, like balls on a billiards table. But when we actually take a minute to reflect on all of it, it’s clearly so much more complex than that.
- acqq 6y ago
  Then you have to watch these videos too: https://xvivo.com/inner-life-of-the-cell/ https://xvivo.com/inner-life-of-the-cell/ For example, this looks like a cartoon but it really behaves so (except that the molecules are too small to have the colors, as in other visualizations): https://www.youtube.com/watch?v=y-uuk4Pr2i8 https://www.youtube.com/watch?v=y-uuk4Pr2i8
- bergstromm466 6y ago
  > marveled at the tiny universe inside our bodies. Could the current change in the sciences be described best as a change from the 'Scientific worldview' to a 'Living systems worldview'? From 'Object-centric reality' to 'Flow-centric reality' (Arthur Brock)[1]? [1] https://youtu.be/2kAgty1aCoA?t=1250 https://youtu.be/2kAgty1aCoA?t=1250 (at around 21:30)
- lbotos 6y ago
  You might like "journey into the microcosmos": https://www.youtube.com/channel/UCBbnbBWJtwsf0jLGUwX5Q3g https://www.youtube.com/channel/UCBbnbBWJtwsf0jLGUwX5Q3g It really reveals a lot of the "small stuff".
- dekhn 6y ago
  I felt this wonder as a kid in a science museum looking through a microscope at tiny bacteria swimming around. I was already a computer hacker at the time, but seeing little state machines that worked in the real world was a revelation. I spent the next 20 years doing a deep dive into molecular machines and indeed, it's marvelous. Viruses, motor proteins, enzymes, all these things do amazing things that humans working in computer science and physics have replicated (often inspired by biology; see What is Life by Schrodinger), demonstrating the universality of information processing. It was a fun excursion, but actually doing engineering on these systems is a nightmare.
axilmar 6y ago
How come, since we know so much, not produce a mechanism that counteracts the virus? how come we only know how to tell the immune system how to react? As a programmer, I suddenly got an urge to learn how I can program proteins to do the stuff I want to do. From reading material around proteins, it seems they are nothing more than mechanical devices.
- hayderado 6y ago
  LOL I had the same reaction, let's program our way out of it. Problem is thought those medical devices aren't as cheap as a MacBook!
- dennis_jeeves 6y ago
  >How come, since we know so much, not produce a mechanism that counteracts the virus? how come we only know how to tell the immune system how to react? I suspect that the reality is that they do not know much, all the rendering/animation give an impression of sophistication and knowledge. Basically deceit.
- rocha 6y ago
  Take a look at how mRNA vaccines work, and how they came to be. It is still mind-blowing to me.
  - ksk 6y ago
    Its a fairly old concept, but we're still not at the stage where it can be used in a product for human use. I work in vaccine r&d (though not as a scientist) and there are many technologies that sound great on paper, but haven't been shown to work in the real world.
- gizmo686 6y ago
  It is quite easy to counteract the virus. The challenge is not causing more collateral damage to the body in the process. We also do have other mechanisms. One of the simplest treatments is convalescent plasma, where you take blood plasma from people who have recovered from a virus (and presumably have antibodies) and give it to an infected patient. This is not telling the immune system how to react in the way a vaccine does; it is bypassing the immune system to provide anti-bodies directly (of course, after the anti-bodies attach, normal immune system responses take over). A team of Isreali scientiest have produced artificial anti-bodies that serve the same function without relying on someone else's immune system to produce [0]. There are also a host of anti-viral drugs designed to interfere with with various processes used by virus. For instance, ribavarin resembles adenoside, which is a one of the building blocks of RNA. It can therefore inject itself into the virus's RNA during replication and cause fatal mutations in the virus. > it seems they are nothing more than mechanical devices. Chemical devices would probably be more accurate. Even determining what shape they have is an difficult computation problem (protein folding). Even if you know that, you have to consider how it would interact with every other chemical process in the body that it comes into contact with. [0] https://www.news-medical.net/news/20200505/Israeli-scientists-discover-monoclonal-antibody-that-neutralizes-SARS-CoV-2.aspx https://www.news-medical.net/news/20200505/Israeli-scientist...
JoeCoo7 6y ago
I'm truly amazed. I enjoyed reading it. My understanding of this virus has increased, but unfortunately it doesn't necessary makes me feel better.

106 points by hayderado 6y ago

While this might come across as a pedantic point, I don’t think CoV-2 comes in via membrane fusion, but it is rather endocytosed (i.e. the receptor is pulled back into the cell, taking the virus with it). This is an important distinction to make, because this opens the door for other opportunities to interfere in this process (e.g. stuffing around with actin dynamics). Of course, this is a pop culture depiction, but I believe that many people discount how useful such visual summaries are for even people who are deep in the field, and as such I’d hope that people spend effort sweating the details, because it does help!

papaf 6y ago
Could it use both methods of entry? https://www.sciencedirect.com/science/article/pii/S0166354220302060#fig3 https://www.sciencedirect.com/science/article/pii/S016635422... I cannot comment on how accurate it is, but I found the interactive overview in the Scientific American to be awesome.
- hirenj 6y ago
  It very well could use both mechanisms, which I neglected to think about. I only think endocytosis is important because that specific mechanism uses ACE2 and heparan sulfate (which can be blocked using heparin I think).
hirenj 6y ago
I had no idea there was more to the page because of the weird scrolling on the site, so I missed the glycan (sugar) stuff, which is my bread and butter. I think the consensus is that there is not likely any shielding going on with the glycans (like what you would find with HIV), but there are glycans that stabilise the ACE2 binding part. Also, people have found glycans on a protein cleavage region, which I would expect could impart resistance to cleavage (a predictor I wrote from a few years back correctly predicted those sites).
- aeternum 6y ago
  Seems like this would be much better as a video. It probably took a tons of effort to put this into a webpage and it was quite buggy and unintuitive.

acqq 6y ago

One of very interesting properties of SARS-CoV (2003) and SARS-Cov-2 (2019) is that they have their "proofreading" replication mechanisms, or in the terms of people working with computers these viruses have an "error correction device" active during the copying that allows them to have a relatively long genome which won't mutate too fast: NYT interactive April 2020, also a good visualization of some "building blocks": https://www.nytimes.com/interactive/2020/04/03/science/coronavirus-genome-bad-news-wrapped-in-protein.html https://www.nytimes.com/interactive/2020/04/03/science/coron... 2015 paper: https://www.pnas.org/content/112/30/9436 https://www.pnas.org/content/112/30/9436 2013 paper: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003760 https://journals.plos.org/plospathogens/article?id=10.1371/j... 2006 paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458802/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458802/

pfundstein 6y ago
Does this slow down it's ability to mutate though, potentially allowing for more effective vaccines?
- acqq 6y ago
  Influenza viruses don't have that mechanism. That doesn't prevent humanity to have working vaccines each year for the currently important influenza viruses. The needed research was already done long ago. But regarding SARS-CoV-2, it's still too early to say anything for sure, we have lost the precious time in not learning enough from the properties of the (2003) SARS-CoV virus, not to mention western world remaining very unprepared for long after the spreading of SARS-CoV-2 started.
  - the_af 6y ago
    What about retroviruses such as HIV, where replication errors are very likely? It's almost like replication errors are a feature of HIV which makes it harder to develop a vaccine (of course, most mutations won't be helpful to the virus, but at least some will). (I'm not saying SARS-CoV-2 is the same case)

gdubs 6y ago

Around the point in the interactive where it shows how the virus swings sugar molecules around to distract the immune system I paused and marveled at the tiny universe inside our bodies. The first time I recall feeling similarly was when I first watched Cosmos as a kid, and Carl Sagan juxtaposes time lapse photography of cities against the bustling activity of cells inside the human body. We walk around every day thinking of ourselves as solid objects in a Newtonian world, like balls on a billiards table. But when we actually take a minute to reflect on all of it, it’s clearly so much more complex than that.

acqq 6y ago
Then you have to watch these videos too: https://xvivo.com/inner-life-of-the-cell/ https://xvivo.com/inner-life-of-the-cell/ For example, this looks like a cartoon but it really behaves so (except that the molecules are too small to have the colors, as in other visualizations): https://www.youtube.com/watch?v=y-uuk4Pr2i8 https://www.youtube.com/watch?v=y-uuk4Pr2i8
bergstromm466 6y ago
> marveled at the tiny universe inside our bodies. Could the current change in the sciences be described best as a change from the 'Scientific worldview' to a 'Living systems worldview'? From 'Object-centric reality' to 'Flow-centric reality' (Arthur Brock)[1]? [1] https://youtu.be/2kAgty1aCoA?t=1250 https://youtu.be/2kAgty1aCoA?t=1250 (at around 21:30)
lbotos 6y ago
You might like "journey into the microcosmos": https://www.youtube.com/channel/UCBbnbBWJtwsf0jLGUwX5Q3g https://www.youtube.com/channel/UCBbnbBWJtwsf0jLGUwX5Q3g It really reveals a lot of the "small stuff".
dekhn 6y ago
I felt this wonder as a kid in a science museum looking through a microscope at tiny bacteria swimming around. I was already a computer hacker at the time, but seeing little state machines that worked in the real world was a revelation. I spent the next 20 years doing a deep dive into molecular machines and indeed, it's marvelous. Viruses, motor proteins, enzymes, all these things do amazing things that humans working in computer science and physics have replicated (often inspired by biology; see What is Life by Schrodinger), demonstrating the universality of information processing. It was a fun excursion, but actually doing engineering on these systems is a nightmare.

axilmar 6y ago

How come, since we know so much, not produce a mechanism that counteracts the virus? how come we only know how to tell the immune system how to react? As a programmer, I suddenly got an urge to learn how I can program proteins to do the stuff I want to do. From reading material around proteins, it seems they are nothing more than mechanical devices.

hayderado 6y ago
LOL I had the same reaction, let's program our way out of it. Problem is thought those medical devices aren't as cheap as a MacBook!
dennis_jeeves 6y ago
>How come, since we know so much, not produce a mechanism that counteracts the virus? how come we only know how to tell the immune system how to react? I suspect that the reality is that they do not know much, all the rendering/animation give an impression of sophistication and knowledge. Basically deceit.
rocha 6y ago
Take a look at how mRNA vaccines work, and how they came to be. It is still mind-blowing to me.
- ksk 6y ago
  Its a fairly old concept, but we're still not at the stage where it can be used in a product for human use. I work in vaccine r&d (though not as a scientist) and there are many technologies that sound great on paper, but haven't been shown to work in the real world.
gizmo686 6y ago
It is quite easy to counteract the virus. The challenge is not causing more collateral damage to the body in the process. We also do have other mechanisms. One of the simplest treatments is convalescent plasma, where you take blood plasma from people who have recovered from a virus (and presumably have antibodies) and give it to an infected patient. This is not telling the immune system how to react in the way a vaccine does; it is bypassing the immune system to provide anti-bodies directly (of course, after the anti-bodies attach, normal immune system responses take over). A team of Isreali scientiest have produced artificial anti-bodies that serve the same function without relying on someone else's immune system to produce [0]. There are also a host of anti-viral drugs designed to interfere with with various processes used by virus. For instance, ribavarin resembles adenoside, which is a one of the building blocks of RNA. It can therefore inject itself into the virus's RNA during replication and cause fatal mutations in the virus. > it seems they are nothing more than mechanical devices. Chemical devices would probably be more accurate. Even determining what shape they have is an difficult computation problem (protein folding). Even if you know that, you have to consider how it would interact with every other chemical process in the body that it comes into contact with. [0] https://www.news-medical.net/news/20200505/Israeli-scientists-discover-monoclonal-antibody-that-neutralizes-SARS-CoV-2.aspx https://www.news-medical.net/news/20200505/Israeli-scientist...

JoeCoo7 6y ago

I'm truly amazed. I enjoyed reading it. My understanding of this virus has increased, but unfortunately it doesn't necessary makes me feel better.