
What's a virus, anyway? The bare-bones basics - chmaynard
https://scopeblog.stanford.edu/2020/04/02/whats-a-virus-anyway-part-1-the-bare-bones-basics/
======
ggm
Wise words a former cell biology aware PhD said to me once: a cell is at a
scale where van der Waals forces means 'water' isn't behaving like you think
and the 'liquid' of a cell is possibly more like a matrix than a fluid. Those
high school cell models are very misleading. He basically said macro scale
intuition was useless for what it means to pierce the cell wall, as an
example. What does "pierce" even mean?

~~~
titzer
Agree! I found ([https://blogs.scientificamerican.com/observations/watch-
the-...](https://blogs.scientificamerican.com/observations/watch-the-life-
cycle-of-hiv-in-colorful-new-detail/)) to be pretty mind-blowing.

~~~
johnohara
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.

~~~
usrusr
> 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.

~~~
johnohara
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.

------
dimtion
Is there a a good read on how RNA and DNA work for a Computer Scientist? And
more generally how biology, genetics, epigenetics, virus, etc work?

Many vulgarization sources say that DNA is like the source code of life. But
they mostly skim across the issue and go to conclusions like "this gene or set
of genes are responsible for that outcome".

But coming from a CS background that sounds a bit like non-sense. I feel like
it is like saying that "this processor instruction is responsible for that
outcome". But in the end what is important is not the individual instruction
but the interaction between them and the environment (Input / Ouput).

~~~
vikramkr
I wouldn't recommend trying to understand it through analogy to CS - I'm a
biologist and know enough CS to feel uncomfortable really using any of the
usual analogies. The problem is that they work ok for a layperson
understanding, but are fundamentally wrong enough that if you want to
understand it at the level of something like virology you'll be lead
constantly astray. I dont know of a better recommendation than "watch some
recorder bio 101 lectures or pick up a textbook, and learn it like a bio major
instead of a CS major." It's a lot of time commitment, but I think you have to
put in the time to actually learn it from first principles.

For context, imagine if I as a biologist asked you, what's a good read on CS
for a biologist? And generally how algorithms, data science, AI, and operating
systems work?

You can understand why it would be difficult to recommend any readings on it.
For me to learn to code at any level, I had to spend the time learning it from
the fundamentals, and it was worth spending the time for me as it was far more
rewarding than trying to wrap my mind around something like "so imagine source
code is this thing that's like DNA + epigenetics + dna topology that codes for
the information you want, but instead of a complex set of chemical and
physical interactions, it's math, and you can change it at will and nothing is
leaky on purpose, and the code you write doesnt evolve unless you tell it to
which you might want to do sometimes for AI stuff, but usually not."

~~~
umvi
It's hard not to draw analogies though.

For example, the covid-19 virus's RNA ends with
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA (33 As) which, as someone pointed out, looks
suspicially like a "NOP sled"[1] (i.e. so that a protein coming in hot can hit
anywhere on the sled and then slide down to the actual information)

[1]
[https://en.wikipedia.org/wiki/NOP_slide](https://en.wikipedia.org/wiki/NOP_slide)

~~~
vikramkr
A poly A tail is at the end of the transcript, not the start. This is a
perfect example of the dangers of analogies because this one is completely
incorrect. Poly A tails protect RNA from degradation. A ribosome will not bind
to that part, it will bind to something within the 5' untranslated region on
the other end of the genome) ribosome binding site, kozak consensus sequence,
etc). If you bound to the poly A tail and slide "down," you'd just slide right
off the end of the gene.

Definitely nothing wrong with trying to find things that look similar across
fields and try and gain differentiated insights, it's certainly an admirable
thing and an important part of making many discoveries. But a first principles
understanding of the structure of DNA, what a 5' end and a 3' end is, and how
transcription/translation works (all bio 101 type stuff) would provide a much
better foundation to do that with. You don't need a degree in biology to know
the basics, just like you don't need a degree in CS to know the basics, but
it's worth learning the basics if you want to get an understanding of the
field or work with it.

[https://en.wikipedia.org/wiki/Polyadenylation](https://en.wikipedia.org/wiki/Polyadenylation)

------
tcgv
> Is a virus a living thing? Maybe.

I remember 20 year ago, at school, when the biology teacher was presenting
this dilemma. Ever since, when I hear someone saying "doing this will kill the
virus", it triggers my brain into this subject, since you can't kill something
if it's not alive ;)

Somewhat related, I also like the concept of the "Viruses of the Mind" [1],
which makes an analogy between the spreading of a biological virus and the
spreading of an ideology.

[1]
[https://en.wikipedia.org/wiki/Viruses_of_the_Mind](https://en.wikipedia.org/wiki/Viruses_of_the_Mind)

~~~
boring_twenties
If you can kill a process, or a proposal I don't see why you shouldn't be able
to kill a virus -- alive or not!

~~~
whatshisface
Process reproduce (through forking) metabolize (stdin->stdout) and maintain
homeostasis (garbage collection). How could they not be alive?

~~~
ethbro
(Morally) Because reproduction without purpose is not life. Necessary but
insufficient.

~~~
daseiner1
what’s the purpose of an amoeba? or a mosquito? or a duck? or a chimpanzee?

~~~
ethbro
Would you not say they each have more purpose than a virus?

~~~
cowboysauce
Definitely not. Viruses perform key roles in ecosystems, particularly in ocean
ecosystems. Their infection and subsequent killing of organisms provides a
vital mechanism for cycling nutrients. They also help keep algal blooms in
check. Viruses kill 20% of bacteria in the oceans everyday.

Viruses also provide a mechanism for horizontal gene transfer. A protein that
is critical to the formation of the human placenta has a viral origin.

Viruses have a massive impact on life, but we're just now starting to realize
it.

~~~
ethbro
Granted, but to me those seem like side effects.

The virus has no intentionality in doing them. They're a consequence of
replication.

In contrast, I think a much stronger case could be made for a chimpanzee,
duck, mosquito, or even amoeba evaluating multiple options, choose one to the
exclusion of others, and pursueing it.

------
trehalose
> Try multiplying a billion billion billion billion by a trillion trillion
> trillion trillion, then multiply that by a thousand, and that (10 to the
> 31st power) is the mind-numbing estimate of how many individual viral
> particles are estimated to populate the planet.

What definitions of "billion" and "trillion" are they using? 10 to the 31st
would be only ten million trillion trillion, going by the common definition of
million as 10 to the 6th and trillion as 10 to the 12th.

~~~
im3w1l
Yeah, if you multiply "a billion billion billion billion by a trillion
trillion trillion trillion, then multiply that by a thousand" you get a larger
number than the atoms in the observable universe.

~~~
civil_engineer
That’s a lot of viruses! I’m staying inside.

------
redindian75
> Is a virus a living thing? Maybe.

Maybe Virus is akin to a SEED. Seeds are inert/dead by themselves, but it
carries as all the code/DNA/instructions needed to spring to life, flourish &
even reproduce infinitely when put in an friendly environment (nourished soil
with water, O2 etc)

~~~
taylorlunt
But a virus doesn't "spring to life." A virus is like a seed that just
generates more seeds without ever making a plant.

~~~
ajna91
The seed analogy may be onto something.

Some viruses don't directly cause the host to create new viruses. Instead they
direct the creation of virus creating factories, which create the virus.

Then you get virophages which are even tinier than normal viruses, which
infect the virus factories of other viruses.

------
js8
What always fascinates me is that biologists talk about how these large
molecules bind and self-assemble, and how enzymes control the reactions and so
forth, but what are the odds? It's almost like putting the parts in the mixer,
and getting your little machine in the output. I have very hard time imagining
it, especially in the cell which has thousands different molecules going on
inside it, how everything gets in the proper place in the end.

~~~
rwmj
Firstly, evolution over billions of years makes it possible. But in more
direct answer to your question about how these things self assemble - at this
level atomic forces are like little magnets (I mean, literally they are the
electromagnetic force) and those cause the atoms to arrange themselves in
particular ways. There are lots of videos online showing this, eg. one I
picked at random:
[https://www.youtube.com/watch?v=muNNSAYZDS8](https://www.youtube.com/watch?v=muNNSAYZDS8)

~~~
acqq
Exactly, molecular self-assembly is completely obvious once one can see the
equivalent with his own eyes.

I hope nobody complains "but he shakes the flask" \-- because that is exactly
what the temperature is -- how fast the particles "jiggle" as Richard Feynman
would that describe:

[https://www.youtube.com/watch?v=K_y5iKcDdOQ](https://www.youtube.com/watch?v=K_y5iKcDdOQ)

------
adam_fallon_
Geohot has been doing a pretty unscientific but interesting look at the
molecular & computational biology side of the coronavirus.

Interesting for coders/hackers

First in the series here:
[https://youtu.be/8vWaawiUteM](https://youtu.be/8vWaawiUteM)

------
refurb
I always thought the "flightosome" picture was a great way that biologists can
demonstrate just how complex biology is.[1]

When you see a biologist draw a system in biology, say, how a protein
interacts with a cell membrane and then causes a change in expression within
the nucleus, it can look relatively simple.

Well, it's about as simple as drawing how an airplane works. In this example,
you have the "flightosome", which is made up of fuselage, wings, cockpit and
landing gear. That's what transports passengers from one airport to another.

Simple right? Well even the landing gear component is complex and with
biology, we have very little understanding of it at all.

[1][https://blogs.sciencemag.org/pipeline/archives/2017/02/01/th...](https://blogs.sciencemag.org/pipeline/archives/2017/02/01/the-
flightosome)

------
titzer
An insanely detailed molecular simulation of HIV infection is extremely
illustrative:

[https://blogs.scientificamerican.com/observations/watch-
the-...](https://blogs.scientificamerican.com/observations/watch-the-life-
cycle-of-hiv-in-colorful-new-detail/)

------
nojvek
Someone who is a molecular biologist, please correct my understanding.

DNA is a molecule, made out of 4 amino acids. ACTG. There are 18 different
kinds of amino acids. Amino acids are made out of carbon, nitrogen, hydrogen,
oxygen. Amino acids make proteins. Proteins are the structural bricks (like
LEGO) that are combined in various sequences by enzymes to build more complex
machinery.

The proteins make up cell organelles, which make up cells.

How much of how DNA turns into proteins and different proteins build different
structures is understood? Do we have a DNA simulator where I can write ACTG
code and it tells me what kind of proteins will be made, how those proteins
will interact to build complex structures?

How close are we for computer science folks to actually start writing
compilers, debuggers, frameworks and simulation tools for DNA and man made
cell machinery ?

How far away are we from making custom DNA + cells that act like 3D printers
taking collagen and building nanometer precision complex structures?

It seems our cells already do nano manufacturing and computation, how do I tap
into that ?

~~~
timy2shoes
DNA is made of nucleic acids (deoxyribonucleic acids), not amino acids. DNA is
translated to amino acids, except when it encodes long-noncoding RNAs, or
miRNAs, or piRNAs, or untranslated regions, or intergenic regions, or
transposons, or psuedogenes.

And the protein coding sequences are coded into proteins, except when there
are alternative splicing sites, or anti-sense RNAs.

And then the protein sequence folds into their minimum free energy state,
except when they are assisted by other proteins, or when they exist as
disordered proteins.

And it's not always DNA -> protein. Sometimes proteins make other proteins,
for example circular proteins can only be made from other proteins.

Then there are post-translational modifications, which change the RNA sequence
between DNA to RNA and RNA to protein. And then there's RNA interference,
where miRNAs interfere with RNA to protein translation.

And then there's epigenetics such as DNA methlyation or histone modifications
(histones are protein which compress DNA) which change what genes can be
expressed when.

Really, for every rule that you've been taught, there is an exception. Biology
is so much more complicated than we understand. And understanding how to make
a biological computer (different from the biological computing of Adelman, yes
the same Adelman as RSA) would involve understanding how all the pieces fit
together.

~~~
omilu
As an outsider, microbiology is hopelessly complex.

------
luxuryballs
Somewhat funny to think how different I would expect an article with this
headline to be if it was posted on HN this time last year.

------
holler
Read this recently and found it fascinating!

[https://en.wikipedia.org/wiki/Viral_evolution](https://en.wikipedia.org/wiki/Viral_evolution)

~~~
boneitis
To add on to sources of fascinating information...

At least for me, I had tons of pedestrian questions, as I haven't taken a
biology/chemistry course since high school.

A search for virology on the youtoobs led me here:
[https://www.youtube.com/watch?v=8_bOhZd6ieM](https://www.youtube.com/watch?v=8_bOhZd6ieM)

I found it to be a homerun in all but addressing my 20-30 questions in these
times just in the first ten minutes. To the point. Without the current yt
culture of gratuitous cuts and FX.

------
lawrenceyan
In the case of the coronavirus, we see a significant binding affinity to the
ACE2 membrane protein, which explains why the infection targets the lungs and
guts so readily.

~~~
koheripbal
And also why common blood pressure medications which block that same receptor
are (probably) and good anti-viral for them.

Losartan is currently in clinical trials for this new usage.

~~~
hpoe
My Dr. said that preliminary results indicate that blood pressure medications,
generally increase your risk with the COVID-19, as well as Ibuprofen.

~~~
jschwartzi
Is this based on basic research or demographic analysis? Has the research
ruled out the possibility that people who are being treated for high blood
pressure are more likely to be older and in poorer shape? Because that's a
pretty strong confounding effect unless the research in question is a
randomized controlled trial.

I've also heard conflicting reports about Ibuprofen. I don't think anyone
knows for sure.

~~~
vladus2000
My initial thought on Ibuprofen is just correlation not causation. How many
people who get a fever will try Ibuprofen to try to lower the fever? Probably
quite a few. When these people die its easy to say "well they all had
Ibuprofen". That doesn't mean it had any effect.

On the flip side, NSAIDs do reduce inflammation and inflammation is part of
the body's response to various stressors; I could see that lowering our
response leads to worse outcomes when sick. I have always thought that cold
medication increases the duration of a cold just from my own observations, so
I do find it at least plausible.

I agree on the high blood pressure, if you are on it that means you have
hypertension and are likely in poorer shape than someone who does not take it.
I can somewhat see diuretics having an impact though as those can flush needed
minerals out of your body when your body is in need. They also dehydrate you,
so if you are on one and don't get properly hydrated and have a proper mineral
balance, I can see that being a big negative.

~~~
djmips
Speculation surrounds ACE inhibitors (ACEI), which are a type of high blood
pressure medication, in that they may dampen your immune response to viruses
over long time usage. The other speculation is that circulating amounts of
ACE2 are increased by ACEI and SARS-Cov-2 specifically binds to ACE2. The
confounding aspects are as you suggest that the overall health including
kidney health are often poorer in people with hypertension.

------
mindfulplay
I find this incredibly fascinating. I wasn't aware of how complex these things
were.

A few videos that blows my mind on what really happens inside your cells -
[https://youtu.be/bee6PWUgPo8](https://youtu.be/bee6PWUgPo8)

[https://youtu.be/Ofd_lgEymto](https://youtu.be/Ofd_lgEymto)

------
olejorgenb
For a deeper dive I'll recommend this lecture series:
[https://www.youtube.com/playlist?list=PLGhmZX2NKiNldpyRUBBEz...](https://www.youtube.com/playlist?list=PLGhmZX2NKiNldpyRUBBEzNoWL0Cso1jip&fbclid=IwAR0dV7y_dk0St28xOmqWLkW1GC4o1YrrZy8RCLWro0q0oTraRq3g7h0fn-g)

------
unexaminedlife
Question: How is the production of a cell wall encoded (or not) in DNA in a
cell's replication process?

------
nojvek
They say there is a part 2. Where is the said part 2, I couldn’t find the
link.

~~~
jmckib
Looks like it hasn't been posted yet. This article came out today, this is the
most recent article from that author, and google didn't turn up anything. It's
strange how the end implies that part 2 already exists though.

------
MichaelMoser123
it's sort of the low level live form is hacking the high level one. am i
missing something?

~~~
jacquesm
Natures pentest, red team edition.

