New broad spectrum anti-viral developed at MIT

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New broad spectrum anti-viral developed at MIT

Postby Telchar » Wed Aug 10, 2011 2:57 pm UTC

http://www.ll.mit.edu/news/DRACO.html

As part of the PANACEA (for Pharmacological Augmentation of Nonspecific Anti-pathogen Cellular Enzymes and Activities) project, researchers from MIT Lincoln Laboratory have developed and demonstrated a novel broad-spectrum antiviral approach, called DRACO (for Double-stranded RNA [dsRNA] Activated Caspase Oligomerizer). DRACO selectively induces apoptosis, or cell suicide, in cells containing any viral dsRNA, rapidly killing infected cells without harming uninfected cells. As a result, DRACO should be effective against virtually all viruses, rapidly terminating a viral infection while minimizing the impact on the patient.

snip

In work reported in the journal PLoS ONE, DRACO was shown to be effective against all 15 viruses that the team has so far tested in cells, including cold viruses (rhinoviruses), H1N1 influenza strains, adenoviruses, a stomach virus (reovirus), a polio virus, dengue fever virus, and several members of hemorrhagic fever arenavirus and bunyavirus families. DRACO was also demonstrated to be nontoxic in 11 different cell types representing various species (e.g., humans, monkeys, mice) and organ types (e.g., heart, lung, liver, kidney). In addition, experiments demonstrated that DRACO not only is nontoxic to mice but also can save mice infected with a lethal dose of H1N1 influenza. Currently, the team is testing additional viruses in mice and beginning to get promising results with those as well.

Dr. Rider says that although more extensive testing is needed, "DRACO has the potential to revolutionize the treatment and prevention of virtually all viral diseases, including everything from the common cold to Ebola." He adds, "Because the antiviral activity of DRACO is so broad spectrum, we hope that it may even be useful against outbreaks of new or mutated viruses, such as the 2003 SARS [severe acute respiratory syndrome] outbreak."


This is awesome. I am concerned about overuse however. Treating everyone with the flue with this is going to lead to resistant strains quickly.
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Re: New broad spectrum anti-viral developed at MIT

Postby The Reaper » Wed Aug 10, 2011 3:23 pm UTC

Reminds me of a comic that came out in Heavy Metal Magazine. They finally cure the last virus, and it was the change that gave us humanity in the first place. Good times.

On the plus side, evolution doesn't work quite like that, but it was still an interesting thought.

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Re: New broad spectrum anti-viral developed at MIT

Postby Glass Fractal » Wed Aug 10, 2011 3:28 pm UTC

I see where this ends. Some harmless virus evolves that gets in all of our cells and people who take DRACO melt or something.

Seriously, though, does it say how the drug figures out which cells have a virus in them?

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Re: New broad spectrum anti-viral developed at MIT

Postby curtis95112 » Wed Aug 10, 2011 3:30 pm UTC

Are there no useful viruses?
It seems like this targets all viruses indiscriminately.
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Re: New broad spectrum anti-viral developed at MIT

Postby aoeu » Wed Aug 10, 2011 3:59 pm UTC

Amazing.

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Re: New broad spectrum anti-viral developed at MIT

Postby Saurus33 » Wed Aug 10, 2011 4:00 pm UTC

Well, bacteriophages are useful, and are the only viable solution I know of to the problem of antibiotic-resistant 'superbugs'. So you couldn't take this and a bacteriophage treatment simultaneously.

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Re: New broad spectrum anti-viral developed at MIT

Postby Angua » Wed Aug 10, 2011 4:02 pm UTC

What about all the DNA viruses?
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Re: New broad spectrum anti-viral developed at MIT

Postby Tirian » Wed Aug 10, 2011 4:11 pm UTC

Glass Fractal wrote:I see where this ends. Some harmless virus evolves that gets in all of our cells and people who take DRACO melt or something.


Yeah, I'm keeping the champagne on ice. CMV is fortunate enough to be a DNA virus, so the fact that it lives in the salivary glands of 40-80% of the world's population shouldn't be an issue, but it certainly suggests that a therapy like this isn't going to work outside the petri dish.

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Re: New broad spectrum anti-viral developed at MIT

Postby Soralin » Wed Aug 10, 2011 6:02 pm UTC

Yeah, this is simply awesome, I mean, isn't cure for the common cold somewhere up there with flying cars and jetpacks and such for future stuff? :) As well as of course a wide variety of other diseases that this could potentially be used for. :)
Tirian wrote:but it certainly suggests that a therapy like this isn't going to work outside the petri dish.

Looks like it's already working outside the petri dish: :)
In addition, experiments demonstrated that DRACO not only is nontoxic to mice but also can save mice infected with a lethal dose of H1N1 influenza. Currently, the team is testing additional viruses in mice and beginning to get promising results with those as well.

curtis95112 wrote:Are there no useful viruses?
It seems like this targets all viruses indiscriminately.

I haven't heard of any useful viruses that I recall, other than ones we might make to kill off a bacterial infection or something, but not anything beneficial that the body harbors itself. And even then, there are broad-spectrum antibiotics that are used, that can kill off beneficial bacteria in the process, but those can always be easily recovered or replaced later, you could do the same with beneficial viruses too if there is such a thing.

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Re: New broad spectrum anti-viral developed at MIT

Postby farnsworth » Wed Aug 10, 2011 6:34 pm UTC

Angua wrote:What about all the DNA viruses?

So far, it only works for double-stranded RNA viruses. Rotavirus, which causes severe diarrhea ("stomach flu"), is one of those.

Something like this should only be used in life-threatening cases to prevent resistance. IIRC some viruses can block apoptosis; if one of the target viruses develops that ability, the antiviral would be useless.

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Re: New broad spectrum anti-viral developed at MIT

Postby Tirian » Wed Aug 10, 2011 6:41 pm UTC

Soralin wrote:Looks like it's already working outside the petri dish: :)


I suppose I meant that slightly metaphorically. Even with lab mice, you know their precise exposure to viruses through exposure or gestation, and so there will never be any surprises. It's hard to imagine the point where they would perform this therapy on a human who is already infected with an inestimable number of human-exclusive viruses, perhaps including ones that will only be discovered when that test subject's major organs are eradicated at the cellular level.

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Re: New broad spectrum anti-viral developed at MIT

Postby Decker » Wed Aug 10, 2011 7:29 pm UTC

Isn't it suspected that mitochondria started out as a different organism? A virus or something? I heard that it has it's own genome.

EDIT: I'm not saying that this will affect mitochondria. I was just going off the discussion of "Useful" viruses earlier.
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Re: New broad spectrum anti-viral developed at MIT

Postby qetzal » Wed Aug 10, 2011 7:55 pm UTC

Very interesting science, but don't get too excited about human applications just yet.

Anyone remember endostatin? That was another protein-based drug that looked even better in mice than this one does (so far). It appeared to completely stop all kinds of different solid cancers from progressing. A company was spun out to develop it, and they spent years and hundreds of millions of dollars attempting to make it work in humans. It never did.

Don't get me wrong - I'd love to see things like this pan out. But it's a long, long way from mice to humans. Most things don't make it, no matter how great they look at first.

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Re: New broad spectrum anti-viral developed at MIT

Postby Shivahn » Wed Aug 10, 2011 8:05 pm UTC

Decker wrote:Isn't it suspected that mitochondria started out as a different organism? A virus or something? I heard that it has it's own genome.

Not viruses, something else. And "suspected" is a pretty weak word for it.

Anyway, I wouldn't be surprised if we had beneficial viruses, but I don't think they'd be beneficial on the scale that mitochondria are. It'd be interesting to see, though.

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Re: New broad spectrum anti-viral developed at MIT

Postby Belial » Wed Aug 10, 2011 8:18 pm UTC

Decker wrote:Isn't it suspected that mitochondria started out as a different organism? A virus or something? I heard that it has it's own genome.

EDIT: I'm not saying that this will affect mitochondria. I was just going off the discussion of "Useful" viruses earlier.


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Re: New broad spectrum anti-viral developed at MIT

Postby Dream » Wed Aug 10, 2011 8:21 pm UTC

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Re: New broad spectrum anti-viral developed at MIT

Postby Iulus Cofield » Wed Aug 10, 2011 8:32 pm UTC

If there was ever a medical breakthrough with an actual chance of killing us all...

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Re: New broad spectrum anti-viral developed at MIT

Postby thc » Wed Aug 10, 2011 8:53 pm UTC

Glass Fractal wrote:Seriously, though, does it say how the drug figures out which cells have a virus in them?


Going simply by the name, the drug binds dsRNA and then activates caspases - which induces apoptosis. Actually, our cells already have a system that does exactly that.

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Re: New broad spectrum anti-viral developed at MIT

Postby farnsworth » Wed Aug 10, 2011 9:02 pm UTC

thc wrote:
Glass Fractal wrote:Seriously, though, does it say how the drug figures out which cells have a virus in them?


Going simply by the name, the drug binds dsRNA and then activates caspases - which induces apoptosis. Actually, our cells already have a system that does exactly that.
Why, then, would we need this drug?

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Re: New broad spectrum anti-viral developed at MIT

Postby justaman » Wed Aug 10, 2011 9:19 pm UTC

farnsworth wrote:
Angua wrote:What about all the DNA viruses?

So far, it only works for double-stranded RNA viruses. Rotavirus, which causes severe diarrhea ("stomach flu"), is one of those.

Something like this should only be used in life-threatening cases to prevent resistance. IIRC some viruses can block apoptosis; if one of the target viruses develops that ability, the antiviral would be useless.

Actually they appear to have tested it on both + and - ssRNA (rhinovirus and poliovirus both +ssRNA, influenza = -ssRNA) and dsRNA (reovirus) as well as dsDNA (adenovirus) viruses. If it is really effective against all of them this is pretty cool.

I think you will find that it works because most viruses have genes that run in different directions through out the genome, and late genes, which are the ones used for packaging of the virus, tend to be transcribed as a "run on" where the RNA polymerase just keeps on transcribing until it falls off the genome. This means that there are overlaps between sequences, and hence dsRNA.

You are quite correct, many viruses can block apoptosis, usually through inactivation of p53, and by forcing the cell into the replicative part of the cell cycle.

I am pretty sure that normal cells produce dsRNA too, though perhaps not enough to activate this drug's pathway.
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Re: New broad spectrum anti-viral developed at MIT

Postby thc » Wed Aug 10, 2011 9:37 pm UTC

farnsworth wrote:
thc wrote:
Glass Fractal wrote:Seriously, though, does it say how the drug figures out which cells have a virus in them?


Going simply by the name, the drug binds dsRNA and then activates caspases - which induces apoptosis. Actually, our cells already have a system that does exactly that.
Why, then, would we need this drug?

Because viruses have evolved ways of disabling and getting around that system?

The journal article* goes into a bit of detail about it. I don't pretend to understand it all, but it seems that the PKR enzyme in our cells detect dsRNA and then there are a bunch of intermediate steps before apoptosis that viruses can f around with. The DRACO enzyme skips directly to the end. I'm also guessing the fact that it is novel is another reason it is so effective and broad spectrum.




*http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0022572

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Re: New broad spectrum anti-viral developed at MIT

Postby Belial » Wed Aug 10, 2011 11:55 pm UTC

justaman wrote:Actually they appear to have tested it on both + and - ssRNA (rhinovirus and poliovirus both +ssRNA, influenza = -ssRNA) and dsRNA (reovirus) as well as dsDNA (adenovirus) viruses. If it is really effective against all of them this is pretty cool.


Aren't the various herpes viruses (chicken pox, mono, oro/genital herpes) dsDNA viruses? And don't they live in your nerve tissue between outbreaks?

I am slightly worried about this antiviral being completely useless due to murdering the nervous system of anyone who's ever had chicken pox.
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Re: New broad spectrum anti-viral developed at MIT

Postby SummerGlauFan » Thu Aug 11, 2011 12:47 am UTC

Belial wrote:
justaman wrote:Actually they appear to have tested it on both + and - ssRNA (rhinovirus and poliovirus both +ssRNA, influenza = -ssRNA) and dsRNA (reovirus) as well as dsDNA (adenovirus) viruses. If it is really effective against all of them this is pretty cool.


Aren't the various herpes viruses (chicken pox, mono, oro/genital herpes) dsDNA viruses? And don't they live in your nerve tissue between outbreaks?

I am slightly worried about this antiviral being completely useless due to murdering the nervous system of anyone who's ever had chicken pox.


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Re: New broad spectrum anti-viral developed at MIT

Postby justaman » Thu Aug 11, 2011 1:00 am UTC

thc wrote:The journal article* goes into a bit of detail about it. I don't pretend to understand it all, but it seems that the PKR enzyme in our cells detect dsRNA and then there are a bunch of intermediate steps before apoptosis that viruses can f around with. The DRACO enzyme skips directly to the end. I'm also guessing the fact that it is novel is another reason it is so effective and broad spectrum.

*http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0022572

Correct. I am not completely convinced of the efficacy of these "drugs" (actually just proteins) yet, it seems that the majority of the treatments were performed prior to, or at the same time as the infection. I would have thought that this would be a problem as I can't see that being an effective system for the majority of potential users, unless they are looking solely to be treating outbreaks and using it as a prophylactic for health workers and people who have potentially been exposed.

Also, as they are just protein based, there will be some stability and delivery issues in vivo.

Belial wrote:
justaman wrote:Actually they appear to have tested it on both + and - ssRNA (rhinovirus and poliovirus both +ssRNA, influenza = -ssRNA) and dsRNA (reovirus) as well as dsDNA (adenovirus) viruses. If it is really effective against all of them this is pretty cool.


Aren't the various herpes viruses (chicken pox, mono, oro/genital herpes) dsDNA viruses? And don't they live in your nerve tissue between outbreaks?

I am slightly worried about this antiviral being completely useless due to murdering the nervous system of anyone who's ever had chicken pox.[\quote]
Yes they are, and do, respectively. I think in those cases, the virus resides in the nerve as a genome (which Field's Virology tells me occurs as a circular molecule), rather than as active virus, so no transcription taking place and therefore no dsRNA. I am not sure how this differs from the active infection though.

edited to fix my url
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Re: New broad spectrum anti-viral developed at MIT

Postby Belial » Thu Aug 11, 2011 1:08 am UTC

Ahh. So it wouldn't be at all effective in curing the various HHV's, but it also wouldn't turn the patient's nerves to paste.

Good to know!
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Re: New broad spectrum anti-viral developed at MIT

Postby Anubis » Fri Aug 12, 2011 4:18 am UTC

Belial wrote:Ahh. So it wouldn't be at all effective in curing the various HHV's, but it also wouldn't turn the patient's nerves to paste.

Good to know!


But if I understand it correctly, it would be effective in preventing outbreaks (although that would require using it fairly often, which would increase the likelihood of resistant viruses evolving).

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Re: New broad spectrum anti-viral developed at MIT

Postby Manial » Fri Aug 12, 2011 8:07 pm UTC

The way I see it, this will never be used for the common cold, at least not in the post-superbug world. But if it works for humans it would be great for the immunocompromised and very elderly/frail.

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Re: New broad spectrum anti-viral developed at MIT

Postby Belial » Fri Aug 12, 2011 11:59 pm UTC

Does resistance to antivirals develop the same way resistance to antibiotics does? I mean, we've been using narrower antivirals to manage herpes and hiv, among others, for quite some time now and generally on a long-term basis for each patient, and I haven't heard anything about resistant strains developing. Granted, I am not captain epidemiology, which is why I'm asking.
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Re: New broad spectrum anti-viral developed at MIT

Postby Shivahn » Sat Aug 13, 2011 12:07 am UTC

Belial wrote:Does resistance to antivirals develop the same way resistance to antibiotics does? I mean, we've been using narrower antivirals to manage herpes and hiv, among others, for quite some time now and generally on a long-term basis for each patient, and I haven't heard anything about resistant strains developing. Granted, I am not captain epidemiology, which is why I'm asking.

HIV is always mutating, though, isn't it? I'm under the impression that very few drugs stay good for very long, and most that do target things that are tougher to evolve, like the reverse transcriptase rather than something else.

Also, I'd assume that herpes doesn't mutate much once it's incorporated into the host genome, but I have nothing to back that up other than the fact that the host DNA protection probably protects it at that point.

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Re: New broad spectrum anti-viral developed at MIT

Postby Arancaytar » Sat Aug 13, 2011 12:30 am UTC

Seriously, "DRACO"? Sounds like something from a zombie outbreak thriller. That's just asking for it.
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Re: New broad spectrum anti-viral developed at MIT

Postby SummerGlauFan » Sat Aug 13, 2011 2:31 am UTC

Shivahn wrote:
Belial wrote:Does resistance to antivirals develop the same way resistance to antibiotics does? I mean, we've been using narrower antivirals to manage herpes and hiv, among others, for quite some time now and generally on a long-term basis for each patient, and I haven't heard anything about resistant strains developing. Granted, I am not captain epidemiology, which is why I'm asking.

HIV is always mutating, though, isn't it? I'm under the impression that very few drugs stay good for very long, and most that do target things that are tougher to evolve, like the reverse transcriptase rather than something else.

Also, I'd assume that herpes doesn't mutate much once it's incorporated into the host genome, but I have nothing to back that up other than the fact that the host DNA protection probably protects it at that point.


I believe that the virus was resisting drugs that directly attack it (basically, the casing became impervious to it); it's not really a targeted process, and the different casings are also why antibodies do not recognize the virus again. This drug targets the cells that are infected (though only by certain RNA processes, which not all viruses use, such as HIV) possibly making an end-run around the adaptions that viruses are capable of making.
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Re: New broad spectrum anti-viral developed at MIT

Postby BaronSweetly » Sat Nov 05, 2011 2:28 am UTC

SummerGlauFan wrote:I believe that the virus was resisting drugs that directly attack it (basically, the casing became impervious to it); it's not really a targeted process, and the different casings are also why antibodies do not recognize the virus again. This drug targets the cells that are infected (though only by certain RNA processes, which not all viruses use, such as HIV) possibly making an end-run around the adaptions that viruses are capable of making.


This is pretty much my understanding as well. Also, as far as I know, viruses don't share genetic material the way that bacteria do, so resistance isn't really much of an issue. Assuming there are viruses that can block apoptosis as mediated by this agent, it's not that other viruses can acquire that immunity from them so much as it is the case that those viruses would be selected for. The issue wouldn't be one of viruses adapting and developing their own immunities, but of other viral infections that were already immune filling the roles left by them in an opportunistic fashion. I wouldn't begin to know how to predict the frequency of such occurrences or what effects this might have. Even if there is no similar side effect, a weakening of humanity's immune system toward viral infections in general as a response to a lack of such threats could still be a possibility. As a whole, I think this is a good thing, though. We may finally have something that could be used in cases such as virulent hemorrhagic fevers that our bodies just can't handle.

Also, to my knowledge, there are not and never have been any viruses that are or were directly beneficial to people. The general modus operandi of viruses (attach to host cell, deliver genetic material, hijack the cell to make more viruses until it explodes) pretty much precludes this possibility. This does not apply to the bacteriophage mentioned earlier, in which case the virus infects and kills bacteria already infecting the patient while ignoring the patient's cells. It also excludes viruses specifically modified for gene therapy, where the harmful genetic material has been replaced with genes to be spliced into patient cells, for instance the viruses used to deliver material to cancer cells to induce apoptosis.

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Re: New broad spectrum anti-viral developed at MIT

Postby Jplus » Sat Nov 05, 2011 11:16 am UTC

Shivahn wrote:
Decker wrote:Isn't it suspected that mitochondria started out as a different organism? A virus or something? I heard that it has it's own genome.

Not viruses, something else.
Alpha-proteobacteria, to be exact. Probably closely related to Rickettsia.
Shivahn wrote:Anyway, I wouldn't be surprised if we had beneficial viruses, but I don't think they'd be beneficial on the scale that mitochondria are. It'd be interesting to see, though.
They are thought to be there, but not in the form of (anything like) virions. They've become incorporated in the eukaryotic genome.

Belial wrote:It was something we ate while we were still single-celled. Not a virus, just another microorganism
It's not entirely sure whether the proto-eukaryote ate the ancestors of our mitochondria. It could also be that the proto-mitochondrion invaded the proto-eukaryotic cell (which wouldn't be strange given the current behaviour of Rickettsia), or that they'd been living in symbiose for a while and the proto-eukaryote had started to envelope the proto-mitochondrion to improve efficiency.
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Re: New broad spectrum anti-viral developed at MIT

Postby Angua » Sat Nov 05, 2011 11:22 am UTC

BaronSweetly wrote:
SummerGlauFan wrote:I believe that the virus was resisting drugs that directly attack it (basically, the casing became impervious to it); it's not really a targeted process, and the different casings are also why antibodies do not recognize the virus again. This drug targets the cells that are infected (though only by certain RNA processes, which not all viruses use, such as HIV) possibly making an end-run around the adaptions that viruses are capable of making.


This is pretty much my understanding as well. Also, as far as I know, viruses don't share genetic material the way that bacteria do, so resistance isn't really much of an issue. Assuming there are viruses that can block apoptosis as mediated by this agent, it's not that other viruses can acquire that immunity from them so much as it is the case that those viruses would be selected for. The issue wouldn't be one of viruses adapting and developing their own immunities, but of other viral infections that were already immune filling the roles left by them in an opportunistic fashion. I wouldn't begin to know how to predict the frequency of such occurrences or what effects this might have. Even if there is no similar side effect, a weakening of humanity's immune system toward viral infections in general as a response to a lack of such threats could still be a possibility. As a whole, I think this is a good thing, though. We may finally have something that could be used in cases such as virulent hemorrhagic fevers that our bodies just can't handle.

Also, to my knowledge, there are not and never have been any viruses that are or were directly beneficial to people. The general modus operandi of viruses (attach to host cell, deliver genetic material, hijack the cell to make more viruses until it explodes) pretty much precludes this possibility. This does not apply to the bacteriophage mentioned earlier, in which case the virus infects and kills bacteria already infecting the patient while ignoring the patient's cells. It also excludes viruses specifically modified for gene therapy, where the harmful genetic material has been replaced with genes to be spliced into patient cells, for instance the viruses used to deliver material to cancer cells to induce apoptosis.

Viruses can and do become resistant to drugs - they can often mutate very rapidly (eg Tamiflu-resistant strains of influenza are now quite common). It's true that they aren't as likely as bacteria to exchange resistances, but it can happen (eg if you are infected with two strains of influenza at once, they can exchange parts of their genome). (eg Tamiflu
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Re: New broad spectrum anti-viral developed at MIT

Postby SummerGlauFan » Sat Nov 05, 2011 4:00 pm UTC

Angua wrote:
BaronSweetly wrote:
SummerGlauFan wrote:I believe that the virus was resisting drugs that directly attack it (basically, the casing became impervious to it); it's not really a targeted process, and the different casings are also why antibodies do not recognize the virus again. This drug targets the cells that are infected (though only by certain RNA processes, which not all viruses use, such as HIV) possibly making an end-run around the adaptions that viruses are capable of making.


This is pretty much my understanding as well. Also, as far as I know, viruses don't share genetic material the way that bacteria do, so resistance isn't really much of an issue. Assuming there are viruses that can block apoptosis as mediated by this agent, it's not that other viruses can acquire that immunity from them so much as it is the case that those viruses would be selected for. The issue wouldn't be one of viruses adapting and developing their own immunities, but of other viral infections that were already immune filling the roles left by them in an opportunistic fashion. I wouldn't begin to know how to predict the frequency of such occurrences or what effects this might have. Even if there is no similar side effect, a weakening of humanity's immune system toward viral infections in general as a response to a lack of such threats could still be a possibility. As a whole, I think this is a good thing, though. We may finally have something that could be used in cases such as virulent hemorrhagic fevers that our bodies just can't handle.

Also, to my knowledge, there are not and never have been any viruses that are or were directly beneficial to people. The general modus operandi of viruses (attach to host cell, deliver genetic material, hijack the cell to make more viruses until it explodes) pretty much precludes this possibility. This does not apply to the bacteriophage mentioned earlier, in which case the virus infects and kills bacteria already infecting the patient while ignoring the patient's cells. It also excludes viruses specifically modified for gene therapy, where the harmful genetic material has been replaced with genes to be spliced into patient cells, for instance the viruses used to deliver material to cancer cells to induce apoptosis.

Viruses can and do become resistant to drugs - they can often mutate very rapidly (eg Tamiflu-resistant strains of influenza are now quite common). It's true that they aren't as likely as bacteria to exchange resistances, but it can happen (eg if you are infected with two strains of influenza at once, they can exchange parts of their genome). (eg Tamiflu


Indeed. As I mentioned, changes to the casing are what cause viruses to resist certain drugs, and fool antibodies. These casings are passed down to the next generation of virus, until another casing mutation occurs.
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Re: New broad spectrum anti-viral developed at MIT

Postby elasto » Sat Nov 05, 2011 4:53 pm UTC

So would this drug theoretically be able to tackle HIV or does that not use dsRNA?

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Re: New broad spectrum anti-viral developed at MIT

Postby Yakk » Sat Nov 05, 2011 5:00 pm UTC

HIV is not dsRNA.
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Re: New broad spectrum anti-viral developed at MIT

Postby Shivahn » Sat Nov 05, 2011 6:32 pm UTC

Specifically, it's single stranded, which increases mutation rate.

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Re: New broad spectrum anti-viral developed at MIT

Postby TheSoberPirate » Sat Nov 05, 2011 6:49 pm UTC

Just wanted to add another point about resistance. It might not be a given that viruses will be able evolve resistance to every type of drug we develop, and a lot probably depends on the drug's mechanism of action. A analogous example might be the use of antibiotics and hand sanitizers and bacteria. While antibiotic resistance is a huge and growing problem, last I heard the ubiquity of alcohol-based wipes and gels was actually found not to be resulting in any resistance. For some reason, all bacteria seem to be equally vulnerable to this, and no resistant strains have yet appeared.

I would guess that no one knows yet how virus populations will be able respond to this particular anti-viral, but the point is that it seems to be theoretically possible to create situations that difficult or impossible for pathogens to evolve out of. Which is an encouraging thought.

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Re: New broad spectrum anti-viral developed at MIT

Postby justaman » Sat Nov 05, 2011 10:11 pm UTC

TheSoberPirate wrote:Just wanted to add another point about resistance. It might not be a given that viruses will be able evolve resistance to every type of drug we develop, and a lot probably depends on the drug's mechanism of action. A analogous example might be the use of antibiotics and hand sanitizers and bacteria. While antibiotic resistance is a huge and growing problem, last I heard the ubiquity of alcohol-based wipes and gels was actually found not to be resulting in any resistance. For some reason, all bacteria seem to be equally vulnerable to this, and no resistant strains have yet appeared.

I would guess that no one knows yet how virus populations will be able respond to this particular anti-viral, but the point is that it seems to be theoretically possible to create situations that difficult or impossible for pathogens to evolve out of. Which is an encouraging thought.

The reason there is no resistance to alcohol based wipes etc, is that these precipitate the proteins inside the bacteria and dissolve the cellular membrane(s), thereby inactivating them totally. To develop resistance, the bacteria would need to convert their whole proteome to ones that are resistant to precipitation by alcohol, which to my knowledge of proteins is totally impossible. Viruses are unable to resist alcohol for the same reasons, but in the case of most viruses, the proteins of the viral coat are self-assembling so they can re-form following precipitation, if the conditions are right. Only a few types of virus contain proteins beside the viral coat proteins.
elasto wrote:So would this drug theoretically be able to tackle HIV or does that not use dsRNA?
Yakk wrote:HIV is not dsRNA.
Shivahn wrote:Specifically, it's single stranded, which increases mutation rate.

Sort of - HIV is a single stranded RNA virus, as Shivahn said, but it still uses cellular mechanisms and the DNA inside the cell to produce its RNA, which would result in dsRNA. Single strandedness by itself does not increase mutation rate - it is the RNA polymerase that is encoded by HIV that causes the mutations. It has quite a high "error" rate, which causes mutations each time it copies the strands. This drug was tested on ssRNA viruses and appears to be effective. However, having actually read the paper, I suspect that it is unlikely to ever make it to actual use due to difficulties in delivery and the fact that they infected and treated at the same time - you would need to take this as a prophylactic for it to be effective, and how many people are willing to do that?
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