St. Quirinus and the Dragon

August 11, 2011 6:08 AM

MIT scientist Dr. Todd Rider has developed a viral infection treatment that works by triggering host cell suicide when it finds the cell has been producing double-stranded RNA. Since dsRNA is the mechanism by which all viral infections proceed, but is not part of normal cellular function, the treatment seems both universal and safe.

From the abstract:

We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells.

We have created DRACOs and shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. We have also demonstrated that DRACOs can rescue mice challenged with H1N1 influenza.

DRACOs have the potential to be effective therapeutics or prophylactics for numerous clinical and priority viruses, due to the broad-spectrum sensitivity of the dsRNA detection domain, the potent activity of the apoptosis induction domain, and the novel direct linkage between the two which viruses have never encountered.

Journalled in PLoS One.

posted by seanmpuckett (49 comments total)

IANA doctor. But that is SO TOTALLY AWESOME. Could it be effective against HIV, theoretically?
posted by omnikron at 6:12 AM on August 11, 2011 [4 favorites]

works by triggering host cell suicide when it finds the cell has been producing double-stranded RNA

1) Why haven't immune systems already thought of this? The double strands aren't inside a cell, right? Or is it that our bodies are just too slow to react, whereas you could be taking one of these things all the time?

2) I sure hope these guys are considering the basic theory of biology when they develop these things. Because this "cure" sounds like a selection pressure for viruses to suppress apoptosis, i.e. increase the cancer rate. You think colds are bad now, how about when they also give you a brain tumor?
posted by DU at 6:17 AM on August 11, 2011 [9 favorites]

IANA doctor either, but this seems like the holy grail of viral research. Thank you for the link.
posted by halfbuckaroo at 6:20 AM on August 11, 2011

I'd love it if a biochemist explained this to us. I read the fuller description here but it still leaves me with a question:

There are already protiens which detect dsRNA disruptions and there are viruses which target dsRNA induced signaling proteins. Likewise, there are viruses that inhibit apoptosis.

So, how is this different? DRACO is just a protein too. Couldn't viruses learn how to disable DRACO too?
posted by vacapinta at 6:20 AM on August 11, 2011 [1 favorite]

DU: Immunes systems have already thought of this. Hence my question. How is this new/different?
posted by vacapinta at 6:21 AM on August 11, 2011 [1 favorite]

We measured the viability of normal human lung fibroblast (NHLF) cells [...] challenged with [...] rhinovirus 1B [...] Untreated cell populations succumbed to virus within days, indicating that any innate cellular responses were ineffective against the virus or blocked by the virus. DRACOs [...] prevented significant cytopathic effects (CPE) in virus-challenged cell populations by rapidly killing any initially infected cells, thereby terminating the infection in its earliest stages. DRACOs had no apparent toxicity in unchallenged cells.

Cure for the common cold! Yay!
posted by CaseyB at 6:21 AM on August 11, 2011

Why haven't immune systems already thought of this? The double strands aren't inside a cell, right? Or is it that our bodies are just too slow to react, whereas you could be taking one of these things all the time?

They have, human cells have mechanisms for triggering apoptosis if they detect dsRNA, but some viruses suppress those mechanisms. (these double strands are inside cells)

I wish them the best of luck getting this to the clinic though, it probably won't be easy.

vacapinta, in principle, yes they could.
posted by atrazine at 6:22 AM on August 11, 2011 [1 favorite]

This is a clever bit of protein design. Quoting from the PLoS article:

In its simplest form, a DRACO is a chimeric protein with one domain that binds to viral dsRNA and a second domain (e.g., a procaspase-binding domain or a procaspase) that induces apoptosis when two or more DRACOs crosslink on the same dsRNA. If viral dsRNA is present inside a cell, DRACOs will bind to the dsRNA and induce apoptosis of that cell. If viral dsRNA is not present inside the cell, DRACOs will not crosslink and apoptosis will not occur.

I see that he has got over a half-dozen patents and patent applications on this technology. It will surely be extremely expensive if it reaches market, if only to recoup the costs of FDA review. If this is as wildly successful as is hoped, I wonder whether illegal backyard protein synthesis and purification labs will be as common as meth labs.
posted by exogenous at 6:23 AM on August 11, 2011 [4 favorites]

exogenous,

Maybe, but the potentially extreme wide applicability of the technique (in the unlikely event that it all ends up working in vivo) means that they make their money on volume. If you can make a couple of hundred bucks per rhinovirus (cold) or 'flu case then that's a lot more money than $50k per case of Ebola.
posted by atrazine at 6:30 AM on August 11, 2011 [1 favorite]

Very interesting but it looks like they are still in the early stages of animal testing, so there are a lot of hurdles to clear before this hits the market. Also I note that it seems to need a parenteral route of administration (in the mice it was given intranasally or intraperitoneally) which presents some additional difficulty in mass-marketing it (although nothing insurmountable).
posted by TedW at 6:31 AM on August 11, 2011 [2 favorites]

It will surely be extremely expensive if it reaches market, if only to recoup the costs of FDA review.

Not if they want to use it to treat the common cold or things like dengue fever that primarily affect developing countries. If this is a truly universal antiviral (and if lab studies show that it doesn't tend to produce resistant strains), then they could sell it pretty cheap and make it up on volume.

The inherent cost of manufacturing a biologic might impose a significant price floor, though.
posted by jedicus at 6:32 AM on August 11, 2011 [1 favorite]

Neat. Hope this isn't the last we hear of this.
posted by Gator at 6:35 AM on August 11, 2011

Hmm... hubristic statement about the elimination of an entire class of diseases, drug called DRACO, induces cell death...

This is TOTALLY not the beginning of a post-apocalyptic horror movie.
posted by condour75 at 6:35 AM on August 11, 2011 [71 favorites]

I can't be the only person thinking "This is how the zombie invasion begins."
posted by kimota at 6:37 AM on August 11, 2011 [17 favorites]

Well, there you go.
posted by kimota at 6:37 AM on August 11, 2011 [5 favorites]

This is TOTALLY not the beginning of a post-apocalyptic horror movie.

What could possibly go wrong!!
posted by odinsdream at 6:37 AM on August 11, 2011 [2 favorites]

(whatever, I'm willing to carry around a wooden stake and hammer if it means the end of this post-nasal drip)
posted by condour75 at 6:37 AM on August 11, 2011 [19 favorites]

I'm thinking, will my health insurance cover it?
posted by Obscure Reference at 6:38 AM on August 11, 2011 [1 favorite]

I would be shocked if the FDA approves something like this as an over-the-counter medication until it has been established on the market for some time, if ever. For one thing, drug delivery problems with a large molecule like this might require intravenous delivery.
posted by exogenous at 6:44 AM on August 11, 2011 [1 favorite]

Thinking the result of this will be superinfections, such as Kalocin in The Andromeda Strain.
Also, doesn't address HIV/AIDS, from what I understand.
posted by Old'n'Busted at 6:45 AM on August 11, 2011

I'm not a virologist but I am a pharmacologist who works with antivirals. The problem is not only having an agent that works in cultured cells, it is getting that agent to the site of action in the organism. Since viruses can go all sorts of places such as the brain is the drug going to get there?
This sounds very preliminary to boost up hopes as of yet.
Also, the statement that all viruses go through dsRNA surprises me - I know of some that do, but I always thought many don't.
posted by dances_with_sneetches at 6:46 AM on August 11, 2011 [1 favorite]

dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO)

How can it not be the beginning of the zombie apocalypse with a name like that? All your opinions are moot in the face of that name. That settles it, I'm buying a pump and some shotgun shells on the way home today. I've already got enough food to last years because of the whole "let's buy this so we can make that" (and we never do) rationale. Bring it on!
posted by RolandOfEld at 6:50 AM on August 11, 2011 [1 favorite]

I can't be the only person thinking "This is how the zombie invasion begins."

You're not.
posted by scalefree at 6:53 AM on August 11, 2011

DRACO - anyone else thinking Deatheater?
posted by arcticseal at 7:00 AM on August 11, 2011 [1 favorite]

How can it not be the beginning of the zombie apocalypse with a name like that? All your opinions are moot in the face of that name. That settles it, I'm buying a pump and some shotgun shells on the way home today. I've already got enough food to last years because of the whole "let's buy this so we can make that" (and we never do) rationale. Bring it on!

Why always the selfish response: thinking only for your own survival? What about your family? Cute children?

Even if it meant prison for the rest of your life, aren't you morally obligated to take prophylactic action?
posted by ennui.bz at 7:07 AM on August 11, 2011

Pffft. The zombie invasion began when the Tea Party arose in response to the efforts to pass a health care reform bill.

If someone could make a vaccine for stoopid then we'd be talking.
posted by spitbull at 7:45 AM on August 11, 2011 [5 favorites]

jedicus: "It will surely be extremely expensive if it reaches market, if only to recoup the costs of FDA review."

Fuck it. If this were the "real deal," I'd be willing (and would rather) to take a very significant tax bump to pay for the development costs.
posted by schmod at 7:46 AM on August 11, 2011 [1 favorite]

Yeah, sorry, this is promising very early stage research. 99% of ideas like this fail. Not saying it's a bad idea or anything, just that it's far too early to tell.
posted by miyabo at 7:47 AM on August 11, 2011 [1 favorite]

Umbrella Corporation already has a patent on this technique.
posted by murphy slaw at 7:49 AM on August 11, 2011 [1 favorite]

"Guama bunyavirus" totally sounds made up to me, as though it would only exist as one of these or as a character in an educational cartoon or something. Of course, the fact that I find it funny probably means that's how I'm going to die.

There's already a Wikipedia page for the drug.
posted by XMLicious at 7:54 AM on August 11, 2011

If it really is a universal antiviral, that would be an incredible gamechanger. But without an effective delivery system, that can pass the blood brain barrier.... well, there's obviously a lot more work to be done.

Most viral infections are systemic, but I wonder if it would be possible to first create treatments that would tackle localized viral infections first.
posted by zarq at 7:54 AM on August 11, 2011

This has nothing to do with zombies, and everything to do with eschatology. We are witnessing the birth of the dragon mentioned in Revelations.

Seriously, could they not think of a less ominous name?
posted by zylocomotion at 7:58 AM on August 11, 2011 [3 favorites]

jedicus: "It will surely be extremely expensive if it reaches market, if only to recoup the costs of FDA review."

For the record I didn't say that. Actually I argued just the opposite: I suspect it will be relatively cheap and the profit made up on volume, particularly in developing countries.
posted by jedicus at 8:01 AM on August 11, 2011

zylocomotion: " Seriously, could they not think of a less ominous name?"

Malfoy.
posted by zarq at 8:10 AM on August 11, 2011 [3 favorites]

Oh good. A nice acronym and everyone jizzes their pants.

dsRNA is present in most cells: the 2006 Nobel Prize was awarded for the discovery on how to study it and it's implications, for f**ks sake.

Unlike most cells, Viruses have LONG stretches of dsRNA , and this appears to be a standard fusion protein approach targeting one thing (long dsRNA) and activiating another (caspase to apoptosis) approach.

It's nice, but MANY other groups have been doing this kind of "target one thing and when that one thing binds, recruit another thing" approach for >10 years. This is why it's in PLOS one and not Nature or Science.
posted by lalochezia at 8:12 AM on August 11, 2011 [6 favorites]

It's nice, but MANY other groups have been doing this kind of "target one thing and when that one thing binds, recruit another thing" approach for >10 years.

So you're saying that there will be multiple zombie apocalypses?
posted by XMLicious at 8:23 AM on August 11, 2011

If multiple zombie apocalypses bring an end to Breathless Glib Analyses of Well-Sold Derivative Dcience, then, please, Eat my brains.
posted by lalochezia at 8:26 AM on August 11, 2011 [2 favorites]

Every thread about an interesting science story that has more zombie than relevant comments is another fantastic piece of evidence how everyone here is above average. The first couple were fine. Now hush while the adults talk.
posted by yerfatma at 8:44 AM on August 11, 2011 [7 favorites]

BGAWSDS is not such a great acronym, lalochezia. May I suggest BYGAWDS (Breathless, Yappy, Glib Analyses of Wheedling, Derivative Science)? That way, you can use the acronym as an interjection whenever discussions like this take place in the future. By gods!
posted by zylocomotion at 8:55 AM on August 11, 2011 [2 favorites]

This is a good idea until you sic it on something like chicken pox - which lives in your dorsal root ganglia. I don't want anything killing off my nerve cells, that shit won't grow back like an epithelial cell will.
posted by caution live frogs at 9:30 AM on August 11, 2011 [2 favorites]

Metafilter: Well-Sold Derivative Dcience.
posted by CynicalKnight at 9:34 AM on August 11, 2011

The singularity has begun!
posted by Renoroc at 9:34 AM on August 11, 2011

I'll do a spiel as a biochemist in a few minutes. For now, AAAAAAAAHHH GAAAAAWD Its a treatment that induces cell death. It doesn't kill the cells directly, it leads the cell to kill itself.

Strikes me as slightly less controllable than what one would want.
posted by Slackermagee at 10:32 AM on August 11, 2011

1) Why haven't immune systems already thought of this?

People have already explained this (the human immune system does utilize it), but it's worth looking, for a moment, into the deeper implications behind your question.

That is, evolution, over millions of years, has an extraordinary capacity for finding solutions to problems. Our mere existence is proof of this; if we were independent observers from outside the universe looking in, how would we ever have determined that something weird like life could be possible just from the properties of physics?

But evolution is, ultimately, random. It can find solutions in large populations over very very long periods of time, but both large populations and very long periods are finite quantities, and thus there is always a chance that solutions that might appear obvious to us might not "occur" to evolution.

The fact that our minds, which are a less random, more systematic (though ultimately limited) method for finding solutions, give us any evolutionary advantage could be interpreted as proof of this.
posted by JHarris at 11:06 AM on August 11, 2011 [4 favorites]

Yeah, I'd like to see some transgenic mice continually expressing the DRACO proteins under normal immune challenge (a few viruses per month). It's possible that the cell death will be no worse than that from the innate and adaptive immune systems, but it needs to be tested.

There are already some decent drugs for many of the viruses that cause colds. A big factor in not approving them is that by the time you show symptoms, it's too late for the drug to do anything. Rhinovirus starts the first wave of replication ~ 8hrs after infection and peaks at ~ 48hrs. By the time you start sniffling and feeling awful, the cold is already being cleaned up.
posted by benzenedream at 11:32 AM on August 11, 2011 [2 favorites]

Every thread about an interesting science story that has more zombie than relevant comments is another fantastic piece of evidence how everyone here is above average. The first couple were fine. Now hush while the adults talk.

Nice try, Sir Edward Ashford.
posted by Celsius1414 at 1:39 PM on August 11, 2011

there is always a chance that solutions that might appear obvious to us might not "occur" to evolution.

Yeah, often because it's effectively off-limits, such as when getting from where-you-are to where-you-need-to-be requires first acquiring some severely negative traits, so evolution will actively avoid that path and miss all solutions that lie down it. While minds, which design with purpose, can think beyond the trough and tap those solutions.
posted by -harlequin- at 5:15 PM on August 11, 2011 [2 favorites]

In a decade, kids will be memorizing his name the same way they memorize Leeuwenhoek, or Pasteur, or Saul, for the invention of the broad-spectrum antiviral.
posted by FormlessOne at 7:53 PM on August 11, 2011

Maybe two decades - it'll take a while to test.
posted by FormlessOne at 7:54 PM on August 11, 2011