Stop squashing your commits. You're squashing your AI too
2 points by jannesblobel 8h ago 7 comments
How can a mutex in Wine be faster than a native one on Linux
3 points by lh_mouse 10h ago 1 comments
Ask HN: Best codebases to study to learn software design?
100 points by pixelworm 2d ago 89 comments
One universal antiviral to rule them all?
161 breve 58 8/26/2025, 2:07:42 PM cuimc.columbia.edu ↗
Given that the article goes on to talk about mild persistent inflammation, is it possible that these individuals are sometimes asymptomatic but still capable of carrying/transmitting viruses at least temporarily? The article talks about potentially immunizing healthcare workers during a future pandemic, but if this was just allowing people to never develop symptoms (and not have to leave work) while having low-grade infections, would we accidentally create a work-force of Typhoid Marys?
It seems that the goal is to learn to trigger the benefits, without triggering the bad parts. Which, should probably have been obvious to you without even bothering to read the article.
[0] https://en.wikipedia.org/wiki/DRACO
DRACO "is a chimeric protein with one domain that binds to viral double stranded RNA (dsRNA) and a second domain that induces apoptosis when two or more DRACOs crosslink on the same dsRNA." (Ridder et al 2011). This article is about packaging mRNA for a set of 10 interferon-stimulated genes that express multiple proteins that target various stages of viral replication.
""" In March 2024 Kimer Med announced it has signed a contract valued at up to USD$750,000 (NZD$1.3 million) with Battelle Memorial Institute (Battelle), the world’s largest independent, nonprofit research and development organization. The contract is focused on the discovery and development of new antiviral drug candidates for the treatment of alphaviruses. """
I'm genuinely asking, I'm a simple software dev not a doctor.
And bacteria self-replicate, whereas a virus needs to infect a cell and be reproduced by that cell. Some antiviral mechanisms attack the reproduction proteins that the human cells use, which the virus cannot do without. And the human cells don't have reproductive pressure to replicate viruses, quite the contrary.
FWIW, I was trained as a bacterial geneticist and routinely used bacteriophage (viruses that infect bacteria) with various resistance mutations.
Viral mutations are not restricted to viruses that infect bacteria.
edit: in fact, fundamental aspects of the genetic code were determined by analyzing and exploiting viral mutations.
https://en.wikipedia.org/wiki/Crick,_Brenner_et_al._experime...
The Crick, Brenner et al. paper that I cited above
* studied mutations in a viral gene called "rIIB"
* the authors used those rIIB mutations to determine that the genetic code was a non-overlapping triplet (now called codons) -- a pretty fundamental discovery.
* What's amazing to me is that they still have NO IDEA what the rIIB gene actually _does_, mechanistically.
It's like learning a little bit about God using an enigma machine (sorry, shitty simile).
And no, strep throat is not worse than ebola.
There’s some ambiguity in their comment because it isn’t obvious what we’re sort of… averaging over, but I think they clearly don’t mean that there no serious viral infections exist.
But so what? Anti-pathogen drugs are useful in the period during which resistance hasn't become universal, and if and when it comes a problem, we'll have other drugs.
Besides: sometimes you get lucky and the virus goes extinct before it can develop resistance (e.g. smallpox)
It's an extreme example, but it demonstrates a fundamental constraint that can't be evolved around. Ideally vaccines can find an equivalent in the space of mechanistic interactions that cut off any evolutionary pathway a virus could reach, either exterminating the virus before it has enough time to complete the search, or by genuinely leaving no pathway even with infinite searching.
Contrary to what you may have heard from Jeff Goldblum life does not always find a way.
2) To further illustrate, some viruses have been nearly eliminated with a single vaccine. Polio didn't manage to adapt before going almost extinct. And a good reason why is:
3) Viruses can only evolve inside contaminated hosts. If you find a cure that stops quickly the virus from multiplying and contaminating, you are also curtailing its ability to adapt. A contaminated host is a giant casino machine, allowing the virus to mutate until it hits a new evolutionary step. A strong enough vaccine or treatment is like throwing out the virus before it has time to play much.
And even worse, some viruses can swap genes if a host has multiple infections at a given time. Bats in particular are known as "hot pots".
Among the symptoms of this disease includes things like necrotic lesions and severe multi-systemic damages.
From what I gather the fact that these people are not more susceptible to viral infections was a surprise. Which probably relates to why the doctors in the parent article were investigating its possible anti-viral properties.
My summary for programmers:
When you get a viral infection, immune cells make a signalling protein called a IFN-1 (Type I Interferon) cytokine, and this flips a boolean flag to True on a bunch of genes (interferon-stimulated genes or ISGs) that produce a bunch of proteins (hundreds) that control the infection. ISG15 is one of them and its role appears to be to downregulate and to limit the inflammation.
The paper title refers to a ISG15 deficiency, meaning if you are dificient in ISG15 that inflamation limitation goes away. But the paper is actually about how in people that naturally have a ISG15 deficiency, there is an always-on low level expression of some of these pro-inflamation genes. So they take that as a safe level.
The did RNA sequencing on experimental ISG15 deficient cells and from heatlhy individuals, identified the mutations, narrowed down to 10 genes (antiviral ones not inhibitors) that in combination significantly inhibited viral replication. They stuck the RNA for such genes in lipid nanoparticles such that they enter host cells, whose ribosomes happily read the RNA like a turing head reads a tape in base 20 and produce proteins encoded by these genes, similar to how the mRNA vaccine works.
So why not dose with the IFN-I directly? Three referenced papers show its "poorly tolerated with significant side effects" and all those downregulators that get expressed limit the inflammation response.
Disclaimer: IANAB (not a biologist) corrections might be due..
I think we'll never have this "one shot," but continue to find tailored treatments for individual conditions. There's no way out of this complexity with "one simple trick," which seems really appealing to the people who determine what gets popular in social media and seemingly politics now. Its just going to be boring and grueling academia and medical trials that are hard for the layperson to understand, hence the important of funding these programs. The recent right-wing election wins and thus a right-wing government cutting all manner of medical grants is supported by the "one weird trick" crowd. Hopefully, the USA will have better leadership in the future to get us back to actual science and to find actual new treatments.
Already, even on HN, the top comments are conspiracy-culture coded, "but, but this one company bought the patent and disappeared with it!" Sigh.
And, yes, it needs to be applied before symptoms start to appear. Otherwise death is almost for certain.
I doubt this research will lead directly to a better vaccine, but having a better vaccine could save a lot of lives.
In fact they're so absurdly specific that while you could bathe in a solution of them and not get sick, they also frequently fail to infect slightly different members of the same species, which is why ultimately they never become antibiotic alternatives: having the right one on hand ranges from difficult to impossible.
There seems to be a lot of information, misinformation, conspiracy theories, and information hiding at least in the perception, if not in reality.
I cannot imagine what society at large will have to deal with or what the reaction will be for or against an “everything” therapy, given what happened with Covid.
The information has not changed dramatically since a few months after its release, and the myocarditis risk was not detected in clinical trials because it is an unbelievably rare event. Detecting it would've required trials orders of magnitude larger than any clinical trial ever.
The biggest negative effect is i've been hearing "you'll be dead in six months from this vaccine" for about 5 years now.
It's been 5 years. have you nothing else going on in your life?
Oh, and here's what the ISG15 deficiency (the condition these mRNAs are there to simulate) does:
> Patients present...with infectious, neurologic or dermatologic features. Basal ganglia calcification is observed in all patients... The basal ganglia calcifications may cause epileptic seizures... The IFN-I inflammation may also manifest early in life as ulcerative skin lesions in the armpit, groin and neck regions. Finally, ISG15-deficiency leads to mendelian susceptibility to mycobacterial disease... [t]hese infections present as fistulizing lymphadenopathies and respiratory symptoms following BCG vaccination.
Yeah, about those antiviral superpowers...
His reputably published, peer reviewed, work can be found here: https://www.science.org/doi/10.1126/scitranslmed.adx5758