New drug developed could cure nearly any viral infection

[Cosmicdancer]

This was reported in PLoS One, a peer reviewed journal. 

New drug could cure nearly any viral infection

Researchers at MIT’s Lincoln Lab have developed technology that may someday cure the common cold, influenza and other ailments.

Anne Trafton, MIT News Office
August 10, 2011

Most bacterial infections can be treated with antibiotics such as penicillin, discovered decades ago. However, such drugs are useless against viral infections, including influenza, the common cold, and deadly hemorrhagic fevers such as Ebola.

Now, in a development that could transform how viral infections are treated, a team of researchers at MIT’s Lincoln Laboratory has designed a drug that can identify cells that have been infected by any type of virus, then kill those cells to terminate the infection.
In a paper published July 27 in the journal PLoS One, the researchers tested their drug against 15 viruses, and found it was effective against all of them — including rhinoviruses that cause the common cold, H1N1 influenza, a stomach virus, a polio virus, dengue fever and several other types of hemorrhagic fever.

The drug works by targeting a type of RNA produced only in cells that have been infected by viruses. “In theory, it should work against all viruses,” says Todd Rider, a senior staff scientist in Lincoln Laboratory’s Chemical, Biological, and Nanoscale Technologies Group who invented the new technology.

Because the technology is so broad-spectrum, it could potentially also be used to combat outbreaks of new viruses, such as the 2003 SARS (severe acute respiratory syndrome) outbreak, Rider says.

Other members of the research team are Lincoln Lab staff members Scott Wick, Christina Zook, Tara Boettcher, Jennifer Pancoast and Benjamin Zusman.

Few antivirals available

Rider had the idea to try developing a broad-spectrum antiviral therapy about 11 years ago, after inventing CANARY (Cellular Analysis and Notification of Antigen Risks and Yields), a biosensor that can rapidly identify pathogens. “If you detect a pathogenic bacterium in the environment, there is probably an antibiotic that could be used to treat someone exposed to that, but I realized there are very few treatments out there for viruses,” he says.

There are a handful of drugs that combat specific viruses, such as the protease inhibitors used to control HIV infection, but these are relatively few in number and susceptible to viral resistance. 

Rider drew inspiration for his therapeutic agents, dubbed DRACOs (Double-stranded RNA Activated Caspase Oligomerizers), from living cells’ own defense systems.

When viruses infect a cell, they take over its cellular machinery for their own purpose — that is, creating more copies of the virus. During this process, the viruses create long strings of double-stranded RNA (dsRNA), which is not found in human or other animal cells.

As part of their natural defenses against viral infection, human cells have proteins that latch onto dsRNA, setting off a cascade of reactions that prevents the virus from replicating itself. However, many viruses can outsmart that system by blocking one of the steps further down the cascade.

Rider had the idea to combine a dsRNA-binding protein with another protein that induces cells to undergo apoptosis (programmed cell suicide) — launched, for example, when a cell determines it is en route to becoming cancerous. Therefore, when one end of the DRACO binds to dsRNA, it signals the other end of the DRACO to initiate cell suicide.

Combining those two elements is a “great idea” and a very novel approach, says Karla Kirkegaard, professor of microbiology and immunology at Stanford University. “Viruses are pretty good at developing resistance to things we try against them, but in this case, it’s hard to think of a simple pathway to drug resistance,” she says.

Each DRACO also includes a “delivery tag,” taken from naturally occurring proteins, that allows it to cross cell membranes and enter any human or animal cell. However, if no dsRNA is present, DRACO leaves the cell unharmed.

Most of the tests reported in this study were done in human and animal cells cultured in the lab, but the researchers also tested DRACO in mice infected with the H1N1 influenza virus. When mice were treated with DRACO, they were completely cured of the infection. The tests also showed that DRACO itself is not toxic to mice.

The researchers are now testing DRACO against more viruses in mice and beginning to get promising results. Rider says he hopes to license the technology for trials in larger animals and for eventual human clinical trials.

This work is funded by a grant from the National Institute of Allergy and Infectious Diseases and the New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, with previous funding from the Defense Advanced Research Projects Agency, Defense Threat Reduction Agency, and Director of Defense Research & Engineering (now the Assistant Secretary of Defense for Research and Engineering


http://web.mit.edu/newsoffice/2011/antiviral-0810.html

[Cosmicdancer]

Sorry this posted several times.  I kept getting an error message that it didn't post when I hit enter.  Please delete the other threads.  Thanks.

[Cosmicdancer]

This article has a little more details.  Researchers tested the drug on 15 viruses, but not HIV.  "So far, the treatment appears safe and non-toxic, and fairly effective when used pre-infection, and in the early stages of infection, for the viruses tested. Whether this general approach will lead to successful treatments for herpes viruses or HIV and other retroviruses, remains to be studied."

http://alfin2100.blogspot.com/2011/08/mit-scientists-unleash-draco-viral.html

10 AUGUST 2011

MIT Scientists Unleash DRACO: Viral Genocide Imminent

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. _PLoS
 
PLoS One: Broad Spectrum Anti-viral

The DRACO antiviral approach created by MIT researchers has the potential to develop into an all-purpose antiviral prophylactic and early-stage treatment. This development is a timely reminder that while microbes can be shifty and clever in avoiding antimicrobial medicines, humans have incredibly creative and resourceful brains -- if they would only use them.

Now, in a development that could transform how viral infections are treated, a team of researchers at MIT’s Lincoln Laboratory has designed a drug that can identify cells that have been infected by any type of virus, then kill those cells to terminate the infection.

In a paper published July 27 in the journal PLoS One, the researchers tested their drug against 15 viruses, and found it was effective against all of them — including rhinoviruses that cause the common cold, H1N1 influenza, a stomach virus, a polio virus, dengue fever and several other types of hemorrhagic fever.

The drug works by targeting a type of RNA produced only in cells that have been infected by viruses. “In theory, it should work against all viruses,” says Todd Rider, a senior staff scientist in Lincoln Laboratory’s Chemical, Biological, and Nanoscale Technologies Group who invented the new technology.

Because the technology is so broad-spectrum, it could potentially also be used to combat outbreaks of new viruses, such as the 2003 SARS (severe acute respiratory syndrome) outbreak, Rider says.

...When viruses infect a cell, they take over its cellular machinery for their own purpose — that is, creating more copies of the virus. During this process, the viruses create long strings of double-stranded RNA (dsRNA), which is not found in human or other animal cells.

As part of their natural defenses against viral infection, human cells have proteins that latch onto dsRNA, setting off a cascade of reactions that prevents the virus from replicating itself. However, many viruses can outsmart that system by blocking one of the steps further down the cascade.

Rider had the idea to combine a dsRNA-binding protein with another protein that induces cells to undergo apoptosis (programmed cell suicide) — launched, for example, when a cell determines it is en route to becoming cancerous. Therefore, when one end of the DRACO binds to dsRNA, it signals the other end of the DRACO to initiate cell suicide.

Combining those two elements is a “great idea” and a very novel approach, says Karla Kirkegaard, professor of microbiology and immunology at Stanford University. “Viruses are pretty good at developing resistance to things we try against them, but in this case, it’s hard to think of a simple pathway to drug resistance,” she says.

Each DRACO also includes a “delivery tag,” taken from naturally occurring proteins, that allows it to cross cell membranes and enter any human or animal cell. However, if no dsRNA is present, DRACO leaves the cell unharmed.

Most of the tests reported in this study were done in human and animal cells cultured in the lab, but the researchers also tested DRACO in mice infected with the H1N1 influenza virus. When mice were treated with DRACO, they were completely cured of the infection. The tests also showed that DRACO itself is not toxic to mice. _Physorg

So far, the treatment appears safe and non-toxic, and fairly effective when used pre-infection, and in the early stages of infection, for the viruses tested. Whether this general approach will lead to successful treatments for herpes viruses or HIV and other retroviruses, remains to be studied.

Since DRACO leads to the death of viral-infected cells, the potential exists that this approach might lead to eradication of "stealth viruses" which hide in particular cell types for a person's entire lifetime.

As for other stealth viruses living inside human cells which have not been discovered by human science, presumably some of these would also be killed by a DRACO-like approach. No one knows what the result of such a broad-spectrum clearance of body viruses might be, because no one knows what these undiscovered stealth viruses are doing in the first place. Assuming they are there, which is quite probable, according to Al Fin system biologists.

[Mycen]

...When viruses infect a cell, they take over its cellular machinery for their own purpose — that is, creating more copies of the virus. During this process, the viruses create long strings of double-stranded RNA (dsRNA), which is not found in human or other animal cells.

While I agree if this is proven true through trials it would be an incredible discovery, I have my concerns that it is not a cure for HIV.  Since HIV lies dormant in the DNA of some cells and is not actively expressing itself, thereby creating RNA for this drug to initiate cell death, it wouldn't eliminate HIV from the body.  Therefore, similar to today's HAART and other treatments, once you stop taking the drug, the virus would reemerge.  I'm hopeful to find when scientists and pharmaceuticals will eliminate the HIV reservoirs.  However, still...this would be incredible.  I do hate the flu and cold and any other nasty viruses.

[Coolio_7]

^^i think once the HIV virus infects a cell even if it is dormant or latent it still ha's to initially injust it's RNA into the host's cell. So this drug targets any cell infected with a virus regardless if the virus is replicating or not.

So I see it working differently than HAART does which targets actively replicating viruses.

[Mycen]

After doing a bit more reading on the subject it seems that may be the case.  We'll have to wait and see what happens after more thorough studies.     But here's hoping!

[John2038]

Sounds huge to me. One of the best news of the Year 2011 (with 2-3 others) on my little personal point of view.

[Coolio_7]

Yes this seems to be a great way of attacking the latent reservoir of HIV. Simply kill all infected cells. But we will have to see with time how this pans out.

There seems to be lots of positive research going on (the scientist who developed the virus attacking a virus-35% efficacy and of course the HIV nanoviricide particles that also seem to show great results). Hopefully some of these will see some large clinical trials soon.