Research Identifies Compounds That Control Hemorrhagic Viruses

People fear diseases such as Ebola, Marburg, Lassa fever, rabies and HIV for good reason; they have high mortality rates and few, if any, possible treatments. As many as 90 percent of people who contract Ebola, for instance, die of the disease.

Facing this gaping need for therapies, researchers at the University of Pennsylvania School of Veterinary Medicine teamed with colleagues to focus on identifying and developing compounds that could reduce a virus’ ability to spread infection. In two studies published in the Journal of Virology, the researchers have identified several prototypic compounds with the potential to one day serve as broad-spectrum anti-viral drugs.

Research Identifies Compounds That Control Hemorrhagic Viruses

"Researchers have identified several prototypic compounds with the potential to one day serve as broad-spectrum anti-viral drugs."

The compounds work in the lab. Next step is animal testing. The compounds control hemorrhagic viruses like Ebola, rabies and HIV. And they do it very differently from other treatments.

Vaccines, other antivirals and antibiotics usually 'attack' the pathogen. These compounds do not target virus cells or proteins - they hone in on host proteins and enzymes. They work by modifying human proteins to prevent viruses from "budding," leaving host cells and infecting more cells. The hope is that slowing down virus budding, and confining the virus buds, will "allow an individual's immune system a chance to develop a robust and a protective response."

Also, 'attacking' pathogens directly is known to promote mutations - the bugs just develop resistance and come back again. These researchers assume that "changing" the host cells (instead of targeting the viruses directly) will short-circuit the pathogens' adaptive response.

It is not known if these compounds will compromise the normal function of the targeted host proteins. However, the researchers hope the benefits of treating an otherwise fatal condition will outweigh potential side effects.


What say you ATS? A miracle-in-the-making, or another molecular-medical nightmare?



The University of Pennsylvania School of Veterinary Medicine led the research teams, and worked with scientists from the U.S. Army Medical Research Institute of Infectious Disease, Thomas Jefferson University and Fox Chase Chemical Diversity Center.

a reply to: soficrow

not sure if its a miracle in the making or not. But the concept is interesting, as it may bypass the adaptive response.

Viral infections and adaptive response is certainly troubling. Bacterial infections and their adaptive response is downright terrifying.

If the novel approach works in viruses, we might see a new era of antibiotics start to occur for bacteria, too.

If they want a real holy grail of medicine, they should go after staph. It is tough bug to kill for a couple of reasons. and it is running rampant in the West as a sometimes untreatable death sentence.

a reply to: soficrow

It is not known if these compounds will compromise the normal function of the targeted host proteins. However, the researchers hope the benefits of treating an otherwise fatal condition will outweigh potential side effects.


What say you ATS? A miracle-in-the-making, or another molecular-medical nightmare?

I think your last lines about potentially compromising the normal function of host proteins and potential side effects could turn into a nightmare, but this should be seen in the animal testing before making it (if it does) to humans.

If it turns out to be successful (without harmful or worse side effects), I think that it could be a great breakthrough.

Even modifying host proteins, could the virus of HIV or the others still somehow adapt and evolve to overcome this?

Other related medical works in progress in different fields are working on replacing just a single chromosome for example.

These could be boons to world health, but do carry some ethical issues as far as how modified does one want their cellular biology changed? Will all this lead to more "playing god" debates?

But as a sort of double standard, personally for me, any way to cure cancer should be explored and implemented as soon as effective means are developed.

I don't make much sense there, do I?

a reply to: bigfatfurrytexan

...the concept is interesting, as it may bypass the adaptive response.

Maybe, but I suspect it simply may trigger another, different adaptive response. ...This seems to be an epigenetic therapy - the compounds apparently hijack and reprogram the epigenetic code. Epigenetic therapies have great promise for chronic disease and a huge variety of other inherited ills. But I'm not so sure we should be messing with our gene expression to combat infectious diseases. ...Still, it could be a great guerilla tactic if normal protein production is not permanently affected. Wouldn't count on it though.

a reply to: soficrow

LOL.

So, essentially, we are screwing up the virus's adaptive response by altering our own (epigenetic)

originally posted by: Chamberf=6
a reply to: soficrow

It is not known if these compounds will compromise the normal function of the targeted host proteins. However, the researchers hope the benefits of treating an otherwise fatal condition will outweigh potential side effects.


What say you ATS? A miracle-in-the-making, or another molecular-medical nightmare?

Even modifying host proteins, could the virus of HIV or the others still somehow adapt and evolve to overcome this?

Maybe - but if the host protein's future production and functionality is not compromised, then it might be a good strategy. Except, like with resistance, researchers would have to constantly develop new compounds. So I'm not sure we'd be further ahead.

Other related medical works in progress in different fields are working on replacing just a single chromosome for example. ...carry some ethical issues as far as how modified does one want their cellular biology changed? Will all this lead to more "playing god" debates?

But ...any way to cure cancer should be explored and implemented as soon as effective means are developed.

I don't make much sense there, do I?

You make sense to me! But fyi - Genetic therapy has not panned out. The new thrust is Epigenetics and most everyone's turning to epigenetic therapies - the epigenetic code being what controls gene expression (the proteins). It's proving to be very successful with cancers and the field is growing leaps and bounds almost daily.

...Again, I see epigenetic therapies as a good way to go for chronic diseases like cancer. Not so sure about using it for infectious diseases though.

originally posted by: bigfatfurrytexan
a reply to: soficrow

LOL.

So, essentially, we are screwing up the virus's adaptive response by altering our own (epigenetic)

Yes. In other words, these compounds mess with our adaptive response to short-circuit the virus' adaptive response.

[The epigenetic code governs the what, when and how of DNA's protein production aka gene expression - it's a kind of "rapid response adaptive mechanism."]

I can see the curing other Hemorrhagic viruses, but honestly I cannot see them actually putting anything out on the market that would cure aids...

With the other viruses they work fast and the death rate is high........theres no money in a short lifespan....

With HIV tho, you can prolong someones life now days almost indefinitely and make money the whole time, because they need to be on the drugs.......

Again I can see a vaccine or cure for the others........for HIV and Aids? nope and thats very sad

a reply to: ManBehindTheMask

Interesting take, made me think: These compounds do NOT kill the viruses - just sequester them inside cells. The hope is that the immune system will have time to figure it all out and kill them off but what if it doesn't? Does that mean victims would need this therapy for life?

originally posted by: soficrow
a reply to: ManBehindTheMask

Interesting take, made me think: These compounds do NOT kill the viruses - just sequester them inside cells. The hope is that the immune system will have time to figure it all out and kill them off but what if it doesn't? Does that mean victims would need this therapy for life?

Could be the case my friend, one never knows whats nefarious and what cant be helped......

But some things just look to easy to exploit, and you can bet if they can they will

unfortunate to say

This makes me ask the question, "Have they exhausted all research with the virus itself?".

In scanning limited information about this, it appears that while it shows sign of success in some primates, there is some doubt as to its efficacy in humans ...

The authors said the findings showed that antibodies could control how the Ebola virus replicated and, crucially, that combining it could also extend the window of time to treat the disease.

Gary Kobinger, one of the study authors, said it was the first time that a combination therapy had been done in non-human primates that showed it could be 100% effective.

“In the past antibodies alone were shown to work 100% only 24 hours after infection, but only 50% after 48 hours,” he said. “Now, with this combination, we’ve reached day three and into day four. For us as a team, it’s a bit of a holy grail to be able to get a 100% when you have clinical symptoms and infection has been detected.”

www.scientificamerican.com...

stm.sciencemag.org...

As well, other strides are being made to identify infected individuals, in the hope of containing the spread of these deadly diseases.

The new tool developed at CDC, an Epi Info viral hemorrhagic fever (VHF) application, speeds up one of the most difficult parts of disease detection: finding everyone that was exposed to, and possibly infected by, someone with a contagious disease. This task, called contact tracing, is an essential step in breaking the chain of disease transmission and ending an outbreak. In addition to facilitating contact tracing, the tool assists with the collection and management of epidemiologic, clinical, and laboratory information for every case. This data is crucial for developing outbreak countermeasures.

www.cdc.gov...

a reply to: InTheLight

The Canadian research you cite is interesting but completely different from the research cited in the OP from Pennsylvania School of Veterinary Medicine teams.

* The Canadian study combines mouse antibodies with interferon (a normal protein made by the immune system) to boost the immune system directly.

* The Penn teams modify human proteins (Tsg101 and Nedd4) to slow virus budding and prevent virus buds from leaving host cells to infect new cells - the immune system isn't boosted at all, just given a chance to "catch up."



Also note: The Canadian research targets Ebola only using mouse antibodies against Ebola - the Penn teams compounds are theoretically "broad-spectrum" antivirals that would work against all or most hemorrhagic fevers.




.

originally posted by: soficrow
a reply to: InTheLight

The Canadian research you cite is interesting but completely different from the research cited in the OP from Pennsylvania School of Veterinary Medicine teams.

* The Canadian study combines mouse antibodies with interferon (a normal protein made by the immune system) to boost the immune system directly.

* The Penn teams modify human proteins (Tsg101 and Nedd4) to slow virus budding and prevent virus buds from leaving host cells to infect new cells - the immune system isn't boosted at all, just given a chance to "catch up."



Also note: The Canadian research targets Ebola only using mouse antibodies against Ebola - the Penn teams compounds are theoretically "broad-spectrum" antivirals that would work against all or most hemorrhagic fevers.




.

From what little I've read so far, Ebola and Marborg are the deadliest, so tackling these with combination therapies and better detection methods would seem the best way to go for further research, instead of venturing into unknown territory, so to speak. Do you not agree?

originally posted by: InTheLight

originally posted by: soficrow
a reply to: InTheLight

The Canadian research you cite is interesting but completely different from the research cited in the OP from Pennsylvania School of Veterinary Medicine teams.

* The Canadian study combines mouse antibodies with interferon (a normal protein made by the immune system) to boost the immune system directly.

* The Penn teams modify human proteins (Tsg101 and Nedd4) to slow virus budding and prevent virus buds from leaving host cells to infect new cells - the immune system isn't boosted at all, just given a chance to "catch up."



Also note: The Canadian research targets Ebola only using mouse antibodies against Ebola - the Penn teams compounds are theoretically "broad-spectrum" antivirals that would work against all or most hemorrhagic fevers.




.

From what little I've read so far, Ebola and Marborg are the deadliest, so tackling these with combination therapies and better detection methods would seem the best way to go for further research, instead of venturing into unknown territory, so to speak. Do you not agree?

I'm still evaluating the options, and do not want to come down hard either for tradition or against "unknown territory." The main argument against new approaches seem to be the unknowns - as in "better the devil you know than the the one you don't?"

Fact is, I'd like to see an entirely new paradigm dedicated to easing assimilation of diseases' into our genetic make-up, which I believe is the "natural" order and would provide all the "immunity" we require. But we're nowhere near that yet.


PS.
1. Do you think the Penn teams' broad-spectrum antiviral would work on MERS?
2. Is there an international competition to make one disease or another the single funding priority?

originally posted by: soficrow

originally posted by: InTheLight

originally posted by: soficrow
a reply to: InTheLight

The Canadian research you cite is interesting but completely different from the research cited in the OP from Pennsylvania School of Veterinary Medicine teams.

* The Canadian study combines mouse antibodies with interferon (a normal protein made by the immune system) to boost the immune system directly.

* The Penn teams modify human proteins (Tsg101 and Nedd4) to slow virus budding and prevent virus buds from leaving host cells to infect new cells - the immune system isn't boosted at all, just given a chance to "catch up."



Also note: The Canadian research targets Ebola only using mouse antibodies against Ebola - the Penn teams compounds are theoretically "broad-spectrum" antivirals that would work against all or most hemorrhagic fevers.




.

From what little I've read so far, Ebola and Marborg are the deadliest, so tackling these with combination therapies and better detection methods would seem the best way to go for further research, instead of venturing into unknown territory, so to speak. Do you not agree?

I'm still evaluating the options, and do not want to come down hard either for tradition or against "unknown territory." The main argument against new approaches seem to be the unknowns - as in "better the devil you know than the the one you don't?"

Fact is, I'd like to see an entirely new paradigm dedicated to easing assimilation of diseases' into our genetic make-up, which I believe is the "natural" order and would provide all the "immunity" we require. But we're nowhere near that yet.


PS.
1. Do you think the Penn teams' broad-spectrum antiviral would work on MERS?
2. Is there an international competition to make one disease or another the single funding priority?

With the virus adaptive (mutative) and symbiotic(?) nature in mind, the Penn team's approach may work, but for how long until the virus "learn" how to circumvent this block until (or if) our immune system antibodies are triggered and coded(?) to erradicate the virus?

I would prefer the team tinker with both our and the virus chemical compounds for a more permanant solution, if that is the way we need to go. Then again, how does natural selection fit into the big picture, what with environmental poisoning, etc.?

Let me summarize: the units of natural selection are DNA, sometimes RNA elements, by no means neatly packaged in discrete organisms. They all share the entire biosphere. The survival of the human species is not a preordained evolutionary program. Abundant sources of genetic variation exist for viruses to learn new tricks, not necessarily confined to what happens routinely or even frequently. The first inklings that genetic recombination could occur at all in bacteria, in F+ E. coli, were at a rate of 10-7, or one in ten million, and one had to look very hard to have any evidence that they existed at all. And some bamboo plants flower only once per century and the careless observer might think that they never recombine. Some generalizations to the limits of genetic change in viruses are equally hasty.

www.pbs.org...

In viewing WHO's statistics regarding global disease mortality, it would appear to me that disease funding is based on a country's economic status, or ability to allocate funding. We see more and more deadly diseases travelling via humans, so I would like to see all countries contributing funds for research into some of the more deadlier diseases.

originally posted by: InTheLight

originally posted by: soficrow

originally posted by: InTheLight

originally posted by: soficrow
a reply to: InTheLight

The Canadian research you cite is interesting but completely different from the research cited in the OP from Pennsylvania School of Veterinary Medicine teams.

* The Canadian study combines mouse antibodies with interferon (a normal protein made by the immune system) to boost the immune system directly.

* The Penn teams modify human proteins (Tsg101 and Nedd4) to slow virus budding and prevent virus buds from leaving host cells to infect new cells - the immune system isn't boosted at all, just given a chance to "catch up."



Also note: The Canadian research targets Ebola only using mouse antibodies against Ebola - the Penn teams compounds are theoretically "broad-spectrum" antivirals that would work against all or most hemorrhagic fevers.




.

From what little I've read so far, Ebola and Marborg are the deadliest, so tackling these with combination therapies and better detection methods would seem the best way to go for further research, instead of venturing into unknown territory, so to speak. Do you not agree?

I'm still evaluating the options, and do not want to come down hard either for tradition or against "unknown territory." The main argument against new approaches seem to be the unknowns - as in "better the devil you know than the the one you don't?"

Fact is, I'd like to see an entirely new paradigm dedicated to easing assimilation of diseases' into our genetic make-up, which I believe is the "natural" order and would provide all the "immunity" we require. But we're nowhere near that yet.


PS.
1. Do you think the Penn teams' broad-spectrum antiviral would work on MERS?
2. Is there an international competition to make one disease or another the single funding priority?

With the virus adaptive (mutative) and symbiotic(?) nature in mind, the Penn team's approach may work, but for how long until the virus "learn" how to circumvent this block until (or if) our immune system antibodies are triggered and coded(?) to erradicate the virus?

I do not think our immune systems "eradicate" viruses - I strongly suspect "developed immunity" is more about integration and assimilation.

I would prefer the team tinker with both our and the virus chemical compounds for a more permanant solution, if that is the way we need to go.

What's permanent in our transient world?

Then again, how does natural selection fit into the big picture, what with environmental poisoning, etc.?

Microbes and viruses respond far more quickly to environmental change than complex organisms - and they "share" their successful adaptations with us.