Why is Delta so infectious? New tool spotlights little-noticed mutation

https://www.science.org/content/article/why-delta-so-infectious-new-lab-tool-spotlights-little-noticed-mutation-speeds-viral-spread

by infodocket • 5 years ago

123 150 5 years ago

science.org

jazzyjackson3• 5 years ago

But because it is stripped of the virus’ RNA genome, it can’t hijack a cell’s machinery to replicate and burst out of the host cell to infect more cells. “It’s a one-way ticket. It doesn’t spread,” says Charles Rice, a molecular virologist at Rockefeller University.

Did these people not take Jurrasic Park seriously? Life finds a way!

shadowgovt6• 5 years ago

Probably best not to extrapolate too much from some fun but inaccurate science fiction when actual human lives are on the line.

The odds of creating a super-virus researching Delta with this method are far, far lower than the odds of Delta continuing to stack up a body-count if we can't understand it better.

jazzyjackson3• 5 years ago

If you want to tell the truth, write fiction.

The odds of COVID19 escaping a BSL4 facility were also pretty low but here we are.

tejtm• 5 years ago

Or that movie where all the wanted posters turned into clones of the outlaws they represent. Hate it when that happens in real life

themitigating• 5 years ago

Remember in TNG when it turned out warp engines damage space?

jazzyjackson3• 5 years ago

Fair counterpoint, but in my defense there really are animals that switch sex when their population is lacking one or the other, so there's not much fictional about it: the scientists were confident in their plan because they didn't know one of nature's tricks.

maxerickson2• 5 years ago

Blue-green algae poisoned the Earth.

(note that my catastrophe actually happened vs being the dilemma of focus in a morality play)

frankfrankfrank• 5 years ago

What I find most shocking about all of this is that we can't even publicly or openly discuss things anymore because even if it is no longer done, there is surely still a latent deterrent effect from all the censorship and public persecution of anyone who was not willing to tow the regime message.

When a culture of fear and intimidation sets it, it is extremely dangerous and usually in my experience even terminal for things like organizations and companies.

kwertyoowiyop4• 5 years ago

Where is it that you’re not able to publicly or openly discuss things? There has never BEEN such a wealth of opinions and discussion freely accessible to everyone.

rsj_hn4• 5 years ago

Correct, which is why there is a such a strong push to get Facebook to increase censorship. All of this communication freedom is absolutely freaking elites out, as their ability to control the discourse has slipped substantially.

ipaddr• 5 years ago

Social media, youtube, the press. Anyplace comments can be censored.

eckmLJE• 5 years ago

I find your comment to be very vague -- what are you talking about exactly?

belltaco• 5 years ago

I blame the rampant misinformation and taking things out of context for that.

public persecution of anyone who was not willing to tow the regime message

What regime? The side that tried to tell us covid was harmless? e.g.

https://www.youtube.com/watch?v=NAh4uS4f78o

ashtonkem3• 5 years ago

… we’re openly discussing this here. What are you talking about?

kordlessagain• 5 years ago

You find it shocking that, even thought it's no longer done, discussing things openly will open up someone to censorship and public persecution?

What did we do 25 years ago to discuss things? It sure the hell wasn't Twitter or Facebook. It was sitting down with the people around us and having a reasonable conversation that didn't include snippets from stupid corners of some webby thing.

It required thought and a reasonable search of the information at hand, which was slower back then. We were more methodical in forming our opinions and what we put our attention on.

brigandish• 5 years ago

I’m all for having a chat with people in real life but all the internet has shown us is here is that we weren’t and are not very methodical in forming our opinions, the speed of incoming information or ability to communicate quicker over distance hasn’t worsened it, it’s just shown up how poor it is. There were plenty of conspiracy theories before Twitter and Facebook.

Regardless, the best method for improving knowledge is making it available to criticism, which is why I favour free speech and openness over this silly culture of “fact checking”, algorithmic censorship and “hate” speech. If it means someone does or doesn’t do something someone else dislikes or thinks is wrong but is legal, like not taking a vaccine, then so be it, they’re adults.

nickthemagicman2• 5 years ago

There's a term for it. It's called Social Cooling.

kwertyoowiyop4• 5 years ago

Can any commenter who actually has a medical degree please indicate this, so we can separate the wheat from the chaff? :-)

bena• 5 years ago

Why would someone with a medical degree be able to verify the works of research biologists?

This comes from a team led by a woman whose credentials in this field are very nearly impeccable.

Not to mention, this article is pretty much information that we have no ability to act on. This is more like something you read and go "Huh, that's interesting" and then move on. It's an indicator that we're learning more. It doesn't need approval from your General Practitioner.

kwertyoowiyop4• 5 years ago

Agree 100%. My reaction was to the comments, not the article itself.

ceejayoz• 5 years ago

People keep making this mistake. A medical degree here is about as relevant as asking a mechanic to opine on metallurgy.

throwaway0a5e• 5 years ago

I see your point but a well practiced mechanic in the right subset of the field (i.e not automotive) is going to have picked up a lot of knowledge to the point where only the most arcane gotchas are likely to get them.

imnotlost• 5 years ago

Maybe Dr. Oz can help! (joking!)

nickthemagicman2• 5 years ago

Medical degree is a generalist. They focus more on pathophysiology than molecular biology.

What you want is a molecular biologist or even better a virologist.

kwertyoowiyop4• 5 years ago

Yes please, a virologist. An epidemiologist too.

zmmmmm• 5 years ago

It's fascinating to see how knowledge evolves over time. So far most of the emphasis has been on the spike protein and its cleavage mechanisms. Now we start to see that may even be a relatively minor factor compared to the nucleocapsid.

It is quite important to understand all these things if we are seeing new variants arise and need to assess how dangerous they are likely to be. Most especially since vaccines are based on the spike protein on the premise that it is essential to the infectiousness. But what if a variant can arise with a highly compromised spike protein yet compensate enough to still be highly infectious due to other factors?

The most interesting thing is to think about where the other empty spaces in our knowledge are that are yet to be filled in - what will we know this time next year that will have us saying "previously we thought ...."

mdp20212• 5 years ago

Forthcoming vaccine Valneva will be based on inactivated virus. Nucleocapsid preserved.

angelzen2• 5 years ago

Novavax has also applied for approval in Canada, UK, Australia and NZ, and possibly already received EUA in Indonesia.

https://news.ycombinator.com/item?id=29111197

https://ir.novavax.com/press-releases?category=2

https://www.forbes.com/sites/joshuacohen/2021/11/03/if-appro...

warning26• 5 years ago

Sinovac and Sinopharm, the Chinese vaccines that may or may not actually work, are also inactivated.

ak2172• 5 years ago

The nucleocapsid is inside the live virus - it's not accessible from the outside. So we don't currently know of a way to train the human immune system to bind to it to kill live virus particles. So while it's important to understand the role of the nucleocapsid in infectivity, it's not actionable for vaccine technology.

Conversely, there is currently no evidence that the spike can be "highly compromised" without reducing infectivity. The spike has to bind specifically to ACE2 in order to enter the cell. As long as that's true, vaccines can continue to target live virus using the ACE2 receptor binding domain in the spike protein.

dekhn5• 5 years ago

I lived through the entire HIV cycle (from first announcements in the press to the current situation).

There weren't really any credible origin stories for HIV for years after the discovery of the virus and the syndrome it causes (AIDS). Eventually (more than a decade later), a reasonably good origin narrative evolved, but not until there were plenty of now-discredited origin theories: https://en.wikipedia.org/wiki/Discredited_HIV/AIDS_origins_t...

jacquesm4• 5 years ago

It's a pretty sobering thought that HIV took 40 years to get to 37 million people confirmed dead, and that COVID-19 took only two years to get to 5 million confirmed dead.

etiam2• 5 years ago

Amazing work, and it would be gratifying to see Doudna bag another Nobel prize, to be awarded in a year when the celebrations aren't markedly subdued by rampant disease.

As important as the posted story demonstrates the N protein to be, it's probably not a good idea to direct a vaccine towards it without a much deeper understanding of the consequences. Derek Lowe's wonderful column in the same magazine touched that point earlier this year, in https://www.science.org/content/blog-post/antibody-dependent...

See the last paragraph under the subheading "ADE and Coronaviruses" for a very brief account of candidate vaccines (against the closely related SARS-CoV) which included the N protein tending to make the disease worse.

For those who have already read that story, but not recently, you may want to check back on it, because I see now that Derek has added an update and more references:

"There was trouble after immunization with a nucleoprotein-directed vaccine, but ADE could also be seen with some of the Spike-directed vaccine candidates as well - see reviews here, here, and here."

Not sure exactly what you, zmmmmm, mean by a "compromised" spike protein, but if it's something like one that is not well neutralized by antibodies raised against epitopes from the early generations of SARS-CoV-2, this post recently would be relevant https://news.ycombinator.com/item?id=29004006

hyperpallium2• 5 years ago

The known is practically nothing compared to the unknown. What we know is inconceivably less than a rounding error.

Appearing to know is essential for our social hierarchies. So... here we are.

rapjr9• 5 years ago

So far most of the emphasis has been on the spike protein and its cleavage mechanisms.

This is something that bothers me about science, why has most of the emphasis been on the spike protein? Has that prevented many researchers from looking for other mechanisms that increase infectiousness? Maybe not in this case, but it seems really difficult to tell what science believes are facts and what are assumptions. I think that if you could identify all the assumptions in science and test them you would find rich material for groundbreaking research. One assumption that seems to be universal is that old science is correct, that it has "stood the test of time", except that often nobody tested it and a lot of it is turning out to be wrong. Those old folk had a tendency to make things up and no one at the time checked them on it because they were an authority unto themselves. I'd like to see any statements that are assumptions specifically highlighted in research papers. There is a little of this in security research papers but not in other research as far as I can tell. How might it be possible to tell how much of "what is true" is actually based on assumptions? Maybe a semantic mining of research papers using an AI could identify assumptions and list them as interesting areas for further testing and research? To start with any statement that doesn't have a citation is a candidate for being an assumption. Also statements like "it is well known" without a citation. Maybe a dependency of logic upon an unsupported statement could be used to find assumptions.

fallingknife2• 5 years ago

From the description it seems like the nucleocapsid protein mutation is something that would make the virus more effective in any given host. Whereas a spike protein mutation would be specific to the host since that is a part of the virus that interfaces with the host cell. In that case I would expect such a protein to already be very optimized (even in a lab leak scenario). Am I missing something here?

ak2172• 5 years ago

The virus evolved in bats, which have a much faster metabolism (to support the metabolic requirements of flight) and a constitutive (always on) immune response. This means in bats, the virus is always "on the run" from the host immune system and the host may never actually completely extinguish the infection, allowing it to continue at a low level while reducing inflammation.

The trade-offs and selective pressures are different in the bat host compared to human. Packaging more copies of the mRNA per particle implies slowing down particle production so more mRNA can be made, but in bat that may slow down the generation time so much that the virus gets extinguished by the always-on host immunity. That's just one plausible mechanism of many, including simply that the protein structure was just not as "optimized" as you expect prior to the spillover event.

rolph• 5 years ago

for general edification:

https://en.wikipedia.org/wiki/Coronavirus_nucleocapsid_prote...

alfor3• 5 years ago

Let’s try in a (safe) lab to make it more infectious, you know for science ! Hey, while we are doing this why not try on MERS, immagine the number of citation I could get for this !

Let’s think for one second the cost of a leak to the world population.

It seems to me that we are doomed to self destruction if we don’t get wiser fast.

jdavis7032• 5 years ago

Viruses will always mutate. We can either let nature beat us to the punch or we can attempt to race nature. Also there’s a lot of literature on BSL 4 labs with crazy safety lapses (e.g. labs using duct tape to seal leaks and what not). If we wanted to treat BSL 4 with the same safety culture of modern nuclear technology we could. This is ultimately a policy problem, not a technical problem (e.g. shutting down dangerous labs and defunding the researchers running offending labs).

etiam2• 5 years ago

Viruses will not always successfully replicate, and failing that, have a hard time mutating. I'm not saying all gain of function research should automatically be precluded, but considering that a severe disease phenotype is (almost?) never directly selected for, deliberately bringing pathogens directly into danger zone is bound to often be go fetching trouble which would never have manifested on it's own.

I'm not convinced I'd feel much more comfortable with biosafety labs being handled according to the same safety culture as modern nuclear technology either, and that's by the argument that they both suffer from the circumstance that policy problems, and policy enforcement problems, do not rank anywhere near the top of a list, good to poor, of how humankind handles things.

travoc• 5 years ago

Don’t forget to lie about it when you get caught.

ashtonkem3• 5 years ago

Yes, virus research does indeed come with trade offs that we have to balance. But it’s not like not researching these things don’t come with trade offs too; after all the worst viral outbreak in human history probably started in Kansas on a farm, not in a lab.

This is an argument for good regulation of safety protocols, not an outright ban.

disambiguation• 5 years ago

i am not an expert, so correct me if i'm wrong..

but not all virus research is "gain of function" right?

what is the advantage of "gain of function" specifically, aside from biowarfare? are we trying to anticipate nature? are there any successful examples?

drran• 5 years ago

SARS CoV research is already banned in USA, so they paid China to do research. It helped China a lot to protect their country.

sethammons• 5 years ago

So the story goes, before the first nuclear detonation, it was not fully agreed upon if the nuclear reaction ignite the whole of the atmosphere and destroy all life on Earth. The final say before giving it a go:

"It is shown that, whatever the temperature to which a section of the atmosphere may be heated, no self-propagating chain of nuclear reactions is likely to be started. The energy losses to radiation always overcompensate the gains due to the reactions."

_is likely_.

https://www.realclearscience.com/blog/2019/09/12/the_fear_th...

Metacelsus• 5 years ago

And keep in mind that they got the lithium-7 calculation wrong (Castle Bravo). What if they had got nitrogen-14 wrong instead?

tzs• 5 years ago

The virus-like things they are making don't have any genetic material. If they get out nothing interesting happens.

To use an analogy with computer viruses, they have the part that given a target system exploits an unpatched vulnerability to load a payload onto the target, but their payload doesn't have the code to scan for other systems to infect.

alfor3• 5 years ago

That is just the first step, after that they did the real thing.

comex• 5 years ago

In this particular case, the mutation being added to the original SARS-CoV-2 is one that was already present in Delta. So if someone were to replicate this with real virus (as opposed to the non-infectious particles the existing experiment used), and the virus were to escape, it seems like the new variant's infectiousness would likely be somewhere between the original and Delta. Which means it would get outcompeted by Delta and the effect on the population would be nil.

There's no guarantee of that, so biosafety is still critical, but as biosafety worst-case scenarios go it seems relatively ho-hum.

alfor3• 5 years ago

The things with scientists (and all humans) is that we ignore what we don’t know.

Virus and humans have billions of year of coevolution.

What we do now with our thinkering with viruses could happen naturally, but it could also take billion of year to happen, or not happen at all.

We have to recognise that the risks of messing with viruses is very high, these are self replicating harm machines.

And if you have one chance in a million of a leak and do a millions of experiment...

mycoborea• 5 years ago

Is there a specific reason as to why the most popular and promoted vaccines in the US target only the spike protein?

SECProto• 5 years ago

Here's[1] a 12 year old paper on why the spike protein is a good target for vaccine development.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750777/

Why is Delta so infectious? New tool spotlights little-noticed mutation

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