Inside the Coronavirus | Hacker News Reader

Inside the Coronavirus

scientificamerican.com

106 pointshayderado22 comments

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.

Then you have to watch these videos too:

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

You might like "journey into the microcosmos": https://www.youtube.com/channel/UCBbnbBWJtwsf0jLGUwX5Q3g

It really reveals a lot of the "small stuff".

> 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 (at around 21:30)

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.

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!

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).

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.

Could it use both methods of entry?

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.

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).

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/coron...

2015 paper:

https://www.pnas.org/content/112/30/9436

2013 paper:

https://journals.plos.org/plospathogens/article?id=10.1371/j...

2006 paper:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458802/

Does this slow down it's ability to mutate though, potentially allowing for more effective vaccines?

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.

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)

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.

> How come, since we know so much, not produce a mechanism that counteracts the virus?

The virus hijacks existing cellular mechanisms for its own purposes. Interfering with those mechanisms could halt the replication of the virus, but it could also kill you. As an example, the virus enters cells through the use of the ACE2 protein. That protein plays a part in regulating blood pressure, so you can imagine the danger that could come from doing playing around with that.

However, SARS-CoV-2 is an RNA virus and its genome codes for an RNA polymerase enzyme that copies its RNA genome. Human cells do not use RNA polymerase and so it could be a target for a drug. This is how remdesivir works, but you have to find a compound that can effectively interfere, but that isn't too incidentally toxic to humans.

> 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.

Good luck, I'd argue that our ability to design functional, non-trivial proteins de novo is essentially non-existent. The function of a protein is highly dependent of its shape and the process of how a string of amino acids folds into the final shape of the protein is extremely complicated and requires supercomputers to simulate. Not to mention that proteins may require help from another proteins to properly fold. Proteins may also be modified after they have folded and a lot of proteins require things like metal ions or other cofactors to actually be functional.

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-scientist...

>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.

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!

Take a look at how mRNA vaccines work, and how they came to be. It is still mind-blowing to me.

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.

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.

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