Wednesday, March 4, 2020

BRIEFING: How viruses work

        I recently had occasion to refesh my memory about the nitty-gritty of protein synthesis, and how viruses capture the resources of a cell to force it to generate the nasty proteins with which they would like to take over the world. I thought it might be appropriate, as we face the possibility of a major global pandemic, to deliver a blog-lecture on the subject. Use this as a reference when the topic comes up in your office or at your dinner-party—you'll have the benefit of telling the true story instead of the panic-story or the conspiracy-story.

[Plugs in laptop, gets Powerpoint up, shows first slide]

        I'll start with DNA, the familiar double-helix nucleic acid. Each of the two complementary strands is made of linked molecules called nucleotides. There are only four to choose from: Cytosine, Guanine, Adenine and Thymine (C,G,A,T) Wherever a C appears in one DNA strand, there must be a G in the complementary strand, and vice versa. Wherever an A appears in one DNA strand, there must be a T in the complementary strand, and vice versa. So a section of DNA, unwound, is schematically like this:

| | | | | | | | | | | | | | | | | | | | | |


        The bonds indicated by vertical lines are not strong, so the helix can and does unwind into two separate strands. One of two things can then happen: either each strand can pick up the nucleotides it needs to make it double-stranded again, in which case it has replicated, OR a slightly different nucleic acid strand may be created using a gene from within single-strand DNA as a template.

        This is messenger RNA, written mRNA, and it's not quite exactly like a single strand of DNA. Where DNA uses thymine, RNA uses uracil, so a strand of mRNA derived from the upper strand shown above would be like this:


        The job of the mRNA strand is to find a cellular structure called a ribosome, which is capable of translating the string of nucleotides into a string of amino acids, which then fold up to become a protein.

        mRNA feeds through the ribosome three letters at a time, each set of three (called a codon) representing one of the 20 possible amino acids according to the genetic code so brilliantly worked out by George Gamow, Francis Crick, Sydney Brenner and others. 

        The leftmost triplet in the string I'm using, AUG, is an almost-invariable START signal, and the amino acid it normally codes for is ignored. Thereafter, this particular string would decode as follows:

A U G | A A C | C U G | U G U | A C G |C U U 
 START          Asn             Leu             Cys             Thr           Leu ....etc...

Here's the entire code, in chart form:

        Notice that, just as AUG means START, there are three codons meaning STOP: UAA, UAG, and UGA. 

         The amino acids are brought to the ribosome packaged with a short RNA strand called Transfer RNA (tRNA), The tRNA molecule presents a triplet of nucleotides to the ribosome for matching to the mRNA strand at its current position. For example, the amino acid Leucine is coded CUG in the above example, in the mRNA sequence. So the tRNA wrapped around Leucine needs to show GAC as a match. This is called an anti-codon.

How viruses exploit this machinery
        Most viruses consist of an RNA strand from a few thousand to a few million nucleotides, coding for between 2 and 2500 proteins. The RNA is wrapped in a protein envelope called a capsid. The virus gains entry into a cell by attaching spikes called peplomers to receptors on the cell membrane. It's unlikely that the receptors are there simply to make life easy for a virus—more likely the receptors have a more benign function that viruses have learned to exploit.

        Once inside the cell, the viral RNA has a few distinct strategies for replicating and being expressed (decoded). I'm going to write about three of these.

Retroviruses use an enzyme called reverse transcriptase to turn themselves into double-stranded DNA, which then inserts itself into the host genome at a random site. The normal machinery of the cell takes over the task of replicating and expressing the viral sequence along with the rest of the genome.

Examples of retroviruses: HIV, HTLV (Human T-lymphotropic virus)

        One technique for gene therapy is to use a disabled retrovirus as a carrier to insert a good copy of a gene into the genome of a patient in whom that gene is missing or incompetent. In principle, a wide range of genetic disease, including some cancers, might be eliminated by this means. However, clinical progress has been slow and some accidents have happened.

Positive-sense single-stranded RNA viruses are the most common form, and include the following list of threats to human health:

West Nile
Common cold

        The descriptor "positive-sense" means that the viral RNA mimics normal mRNA perfectly, with all codons reading correctly including the start and stop sequences AUG and UAG. A coronavirus is about 30,000 nucleotides long in total. So the (+)ssRNA goes straight to a ribosome and says "translate me." The ribosome obediently churns out proteinnote 1, and one of the first proteins produced is an enzyme that assists in replication of the viral RNA itself.

        To make things even worse, (+)ssRNA keeps the ribosomes so busy that normal protein synthesis is inhibited.

Negative-sense single-stranded RNA viruses are the same but written backwards. Before they can be expressed, they first have to be converted to positive-sense by RNA polymerase. These viruses are in general much more complex than the (+)ssRNA type, and generate capsid-enveloped copies of themselves that then extrude from the cell and go off to do further damage to other cells.

Notable examples of (-)ssRNA viruses are:


How do viruses learn these tricks?
        Of course, viruses could not possibly have evolved as external to cells—"knowledge" of how protein synthesis works would be essential for a virus to develop a way of exploiting it.

        In my opinion, viruses must have originally evolved within cells and later been ejected, or the co-evolving cells died off leaving the viruses as evil survivors. If that's correct, (-)ssRNA would be the original form and the other types evolved later from that form. There's even a theory that viruses evolved as the first living forms, and more complex entities followed along.

Extraterrestrial life?
        Knowledge of these detailed living processes makes me a skeptic when it comes to the question of life elsewhere in the universe. As we learn more about how common planetary systems are, people say "with all those trillions of possible sites where life could have evolved, it's ridiculous to think that planet Earth is the one and only place it actually happened."

        I say no, it's not ridiculous at all. The intricacy of the processes I have described in this blog-lecture is such that, to me, it could only happen once in this particular way. If there is a form of extraterrestrial life somewhere, it would have to have its own rules  and its own chemistry. I doubt if we'd even recognize it as life if we had a sample of it.

Could some of these viruses be artificial?
        In other words, the question is "could some laboratory have created and released coronaviruses as a biological weapon, or a deliberate population-reduction strategy?" 

I don't know. I doubt it. Ken Cuccinelli, acting deputy secretary of the Department of Homeland Security, recently said this:
 "I will say the reading that I have done of medical professionals suggest that the structure of the virus seems unlikely to have been man-made because if it was made to be a threat, you would expect to see certain characteristics that aren’t present.
I have no idea what he meant by "certain characteristics."

 This analysis might be helpful.

=====================/ \====================
[1] The ribosome delivers all the protein encoded by the viral RNA connected up in one long chain. A biochemical called a protease chops that chain up into functioning protein packages. One strategy that has already had some success against the HIV virus is to find a way of attacking viral protease, disabling it and thus thwarting the virus's life cycle. Anti-viral drugs that perform this trick are called Protease inhibitors, and an inhibitor effective against coronavirus is a subject of intensive research.


Unky Monkle said...

As a kid back in the '60s, I once read an article in Reader's Digest, that the Flu might be a form of communication from an extraterrestrial source.

Binaryspellbook said...

Hello old friend. I am in lockdown and it is driving me crazy. But I am ok. No word yet when my school will open. Latest word is that Universities will be closed until May first.

expat said...

For those who don't know, "binaryspellbook" is a Scottish design engineer who went to Beijing to teach small kids --what? 5 years ago? More?

He and his missus were champion tweakers of Richard Hoagland back in the day.

Chris Lopes said...

Welcome back Binaryspellbook. Glad to hear you're ok.

"He and his missus were champion tweakers of Richard Hoagland back in the day."

That was back when Hoagland was worth tweaking. :)

Anonymous said...

Ken Cucinelli is a nut who wanted to make oral sex illegal as Virginia Attorney General.

Binaryspellbook said...

Aye Expat, going on five years. Hi Chris....that was when Hoagland was worth teaking. Funny bro. Hope you are well. I have don my mask and do the great escape to the one wee shop I know is open if I want a cold beer and some noodles. The family are my friends so they will risk selling to me. It is nuts here. Streets shut off, checkpoints everywhere taking your temperature. Give me your papers. I figured out early on not to speak Chinese..I just play the dumb foreigner.

expat said...

Very interesting. I sure hope that isn't a picture of our near future, but it could be.

Two Percent said...


Many thanks for this briefing. Excellent work, spoiled somwewhat by the inclusion of this:

"... the virus seems unlikely to have been man-made because if it was made to be a threat, you would expect to see certain characteristics that aren’t present.”

This is a type of logical fallacy or misleading argument stratagem. I have a couple of books in storage which would probably provide the official name for it, but I'm not going to that much trouble.

Let me explain it thus. The question of whether or not the virus was artificially created is a broad one. Assuming for the time being that it was, there could be many possible reasons or intentions behind it. These could include, as I say, that it is a population reduction tool. This doesn't mean it's a threat. A threat has been defined as:

a declaration of an intention or determination to inflict punishment, injury, etc., in retaliation for, or conditionally upon, some action or course; menace

There's little to indicate that the new coronavirus(es) were or are any kind of threat, simply because if it/they were, then the threat has already been carried out - the virus has been released and is spreading around the entire planet faster than the Aussie bush fires. A threat that has been enacted cannot therefore by definition continue to be a threat.

So, what Ken Cucinelli (whose name sounds Italian, so may be as crazy as the rest of them) attempted to do was narrow the range of possibilities with a spurious argument - a Red Herring - to distract his audience (from the more frightening possibilities, perhaps). He sought to narrow the discussion to an area that is insignificant if not meaningless. The guy is, in effect, a politician anyway.

In reality, the virus may well have been man-made, for the purpose, not to threaten China (an extremely dangerous game), but to make a very potent First Strike, intended to cripple their economy and severely curtail their military and territorial ambitions.

Alternatively, it may have been made by "Higher Powers" to reduce the population here on Earth, to slow its inevitable destruction by us foolish, reckless and selfish humans.

The "certain characteristics" is another Logical Fallacy. This one is known as a False Call to Authority, in which KC tries to imply that he knows something we don't - which you admit:

I have no idea what he meant by "certain characteristics."

Nor do I, but of course, that is the intention of this logical fallacy.

expat said...

« In reality, the virus may well have been man-made... »

That's no better than Hoagland's narrative about the hurricane that stalled over the Bahamas. Both propositions have the following form:

1. B happened
2. A is among the possible causes of B
3. A assumes an extremely powerful conspiracy with evil intent
4. Therefore A caused B

Binaryspellbook said...


The English are feeling the pinch in relation to recent virus threat and have therefore raised their threat level from “Miffed” to “Peeved.” Soon, though, level may be raised yet again to “Irritated” or even “A Bit Cross.”

The English have not been “A Bit Cross” since the blitz in 1940 when tea supplies nearly ran out.

The virus has been re-categorized from “Tiresome” to “A Bloody Nuisance.” The last time the British issued a “Bloody Nuisance” warning level was in 1588, when threatened by the Spanish Armada.

The Scots have raised their threat level from “Pissed Off” to “Let's Get the Bastard.” They don't have any other levels. This is the reason they have been used on the front line of the British army for the last 300 years.

The French government announced yesterday that it has raised its alert level from “Run” to “Hide.” The only two higher levels in France are “Collaborate” and “Surrender.” The rise was precipitated by a recent fire that destroyed France's white flag factory, effectively paralyzing the country's military capability.

Italy has increased the alert level from “Shout Loudly and Excitedly” to “Elaborate Military Posturing.” Two more levels remain: “Ineffective Combat Operations” and “Change Sides.”

The Germans have increased their alert state from “Disdainful Arrogance” to “Dress in Uniform and Sing Marching Songs.” They also have two higher levels: “Invade a Neighbour” and “Lose.”

Belgians, on the other hand, are all on holiday as usual; the only threat they are worried about is NATO pulling out of Brussels.

The Spanish are all excited to see their new submarines ready to deploy. These beautifully designed subs have glass bottoms so the new Spanish navy can get a really good look at the old Spanish navy.

Australia, meanwhile, has raised its alert level from “No worries” to “She'll be alright, Mate.” Two more escalation levels remain: “Crikey! I think we'll need to cancel the barbie this weekend!” and “The barbie is cancelled.” So far, no situation has ever warranted use of the final escalation level.

The Russians have said “Its not us”

Two Percent said...

C'mon expat,

You can do better than that - though this is slightly better than the earlier "you're guessing."

If you'd care to link your As and Bs to the relevant elements of my proposition, I'd look at it (especially the "extremely powerful conspiracy with evil intent" bit), but I'm not guessing WTH you're trying to say/show.

I'm not even claiming my comments as facts, just realistic possibilities, so what's your real issue with them?

Maybe, the truth is, no one with a long-held, fixed worldview likes to have it challenged or disturbed?

Anyway, please feel free to dismantle my argument and expose the flaws. None of this A and B nonsense, please. And tarring me with the Hoagland brush is a little offensive.

Two Percent said...


What would be so "evil" about releasing a virus that impartially kills off the old, the sick, the weak, diseased and the self-abused unhealthy among humanity, as part of a plan to save us from our otherwise inevitable self-destruction?

Surely, saving us from ourselves by cutting off a pile of dead wood has to be a good thing...

We kill and cull animals, we prune and cut and harvest trees, for the betterment of the remainder. What's the difference?

Dee said...

"2. A is among the possible causes of B"

There's also this well known "woo" factor of weird or suspicious looking coincidences. They need to be appreciated but at the same time acknowledged to be often near meaningless when used in hindsight. Because there might always be "something" in any complex environment that is odd but it's important to phrase the research beforehand and not scan for all possible oddities after the fact occurred.


- The only lab in whole China working on deadly viruses (highest bio-safely level or BSL-4) is remarkably near that "food market" which was possibly ground zero or closely related to it. Not sure about distance, 30 km?

- The Porton Down chemical weapon facility was 8 km outside Salisbury where exotic nerve gas was found to be used on a former Russian spy and some other bystanders.

Now for the latter I could supply a theory using Porton Down. Like the mysterious Anthrax case in the US, a disgruntled and mentally disordered scientist could have taken a sample out because he wants to start WW3. Everything else would then be unrelated to the poisoning.

For the Chinese virus, a scientist might have been infected inside the lab and carried it in his free-time to the food market.

Note that these examples do not require any "extremely powerful conspiracy with evil intent" and therefore way more reasonable suspicions which will be hard to exclude completely, at this stage. Reality can be more bizarre than our imagination and research combined!

expat said...

« please feel free to dismantle my argument and expose the flaws. None of this A and B nonsense, please. »

That's an invitation to go round and round in polemical circles. Declined.

Two Percent said...

And this:

"That's no better than Hoagland's narrative about the hurricane that stalled over the Bahamas. Both propositions have the following form:"

is not polemical? In reality, who's inviting who here?

To the contrary, mine was an invitation to demonstrate to us all that your earlier polemical allegation and odious comparison were valid and deserved.

Anyway, since you decline, I accept that you have no case.

Apology accepted.