The GP is right in that our intuitions aren't cutting it down at the bottom.
All these animations tend to edit out the water molecules so that the audience can understand better. The proteins aren't colored blobs at all. At these scales you'd clearly see individual atoms instead of blobs. But watching a bunch of really detailed atomic ball-stick models would be confusing. And not only are the H2Os battering everything like TIE fighters in the Hoth asteroid field [0], there are ions in there too (Na, K, Cl, etc) that really effect the cell. The membranes are also edited, as many cells are porcupined with receptors like an over crowded wave pool [1]. In addition to the water/saline being edited out, most of the other proteins, vesicles, and interior membranes are also gone for the sake of clarity. There is nearly no free 'space' in the cell, think of a really crammed subway car [2], with the air being like the water/saline. But only much much tighter.
The cell is more like a frantically efficient liquidy crystaly thingy than a wonky wobbly blobby poofed-up juice box. And each one is utterly deeply profoundly fascinating.
I think David Goodsell's beautiful paintings, in his book Machinery of Life, were the first serious attempt to depict how crammed a cell is (page down past the pictures of individual molecules to get the the cell cross-sections):
The other thing missing from those videos is any indication of how random these processes are. At one point, an actin filament assembles by having monomers fly directly at the tip and stack neatly together. It's not like that. In reality, there are all sorts of molecules just randomly moshing around, and occasionally, an actin monomer will bump into the tip of the filament and stick, because it has a binding site. But sometimes one will bump into the tip and not stick! Sometimes, the tip of the filament will fall off! The growth is purely statistical: monomers are more likely to stick than to fall off, and more likely to stick than some random unrelated protein is to stick.
Pity I only get 1 upvote. I'd triple-click if I could.
This animation enables one to visualize a single SARS-CoV-2 virion binding with the ACE2 enzyme, entering the host cell, and replicating 4-5 new virions.
One SARS-CoV-2 virion is 125 nanometers wide. By the time it shows up on a CT scan we are talking many, many billions.
It's seems impossible anyone could test positive and still be asymptomatic.
> It's seems impossible anyone could test positive and still be asymptomatic.
Why? Most symptoms are part of the body's response switching into overdrive and not a direct consequence of cells getting subverted into virion farms. If the immune system wins without resorting to state of emergency measures like a fever you won't notice, but in the meantime there is a phase of viral replication in the throat.
With SARS-Cov-2 there is even the pattern that detection drops already in the throat of patients that still have a pneumonia raging in their lung (probably because the throat, as a battlefield in this war, somehow favors the immune system more than the lung?), so it's not even a subset/superset relation between symptoms and positive throat PCR, it's a partial overlap.
Seems impossible but from observation obviously is not.
Comorbidity is the issue with SARS-CoV-2. It is interesting that some patients testing positive report losing the sense of taste and/or smell while others report digestive problems prior to the onset of acute respiratory problems or even sore throat.
I note that the virus depicted in the animation is HIV. How much of the lifecycle is different from HIV to SARS-CoV-2? One thing I noted is that it said the inserted viral DNA might remain dormant for years; surely that part is HIV-specific? (Or do we really bear viral infections for years after recovery, and—I presume—rely on the continued presence of antibodies to quash the remaining DNA?)
That part is mostly specific to retroviruses and DNA viruses. Retroviruses are special because even though they are RNA based they can "translate" their RNA into dna once inside the cell and embed that DNA into the cell's genome. That translation in itself is remarkable since it's the opposite of the normal DNA to RNA "translation" we see in almost every organism, hence the "retro".
DNA based viruses don't have that unique mechanism but the result is conceptually the same: you get a virus that is extremely hard to completely cure/remove due to it being present in some of your own DNA. Herpes is a DNA based virus and that's why you can't ever be fully cured from it.
That's also why retroviruses like HIV can only be suppressed. It's also why antiretroviral drugs try to inhibit the replication phases of the virus, which makes managing the disease possible but can't remove the virus itself. Still, a cocktail of those inhibitors is an amazingly powerful treatment against AIDS and leads to HIV becoming basically dorment in the body.
A ribovirus (which is what coronaviruses are) is RNA based but it doesn't embed itself into our genome. It never translates it's RNA and since RNA is fundamentally less stable of a molecule than DNA, you get really high mutation rates. That "instability" is caused by the lack of a built in error checking mechanism in RNA. Those random mutations are part of why Influenza is hard to build immunity against. But it's also why RNA based viruses are generally either too virulent and mortal to allow for effective spread, or rapidly evolve towards less lethal forms.
Keep in mind that I've generalized a lot and that there are a lot of exceptions and outliers when it comes to viruses. For example, Hepatitis C is a ribovirus but it has a special protection mechanism that protects it's core genetic material from mutations even if it's RNA based.
> It never translates it's RNA and since RNA is fundamentally less stable of a molecule than DNA, you get really high mutation rates. That "instability" is caused by the lack of a built in error checking mechanism in RNA.
The coronovirues have a proofreader mechanism, which is interesting.
Yep! That's what really makes influenza special, as I said the mutation rates are only part of why Influenza viruses rapidly change. Their ability to cross between species by combining easily with other types of influenza viruses are the key to their incredible variability
One of the distinguishing trait of CoVs are their special RNA replication/transcription mechanisms that results in less errors, which is really important considering the large size of their genomes compared to other RNA based viruses. Though, and correct me if I'm wrong, aren't they still extremely less stable than DNA viruses? Which is why only short/medium term immunity is usually possible? I don't know a lot about the synthesis of coronavirus RNA but it looks super interesting
> Though, and correct me if I'm wrong, aren't they still extremely less stable than DNA viruses?
That's correct. Worse, the proofreader doesn't have to protect all parts equally...
> Which is why only short/medium term immunity is usually possible?
No. For some viruses active immunity just doesn't last particularly long for reasons we don't understand (or at least it was described as not understood in every paper I've seen on the subject). For some viruses you can be reinfected months later with exactly the same virus. This is the case for several cold causing viruses.
Amazing. The mind boggles at how complex this is and the fact that humans have the tools to discover and understand the process. Thank you very much for sharing!
