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TMFBlacknGold (99.03)

Experimental Drug Could Defeat Any Virus

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August 12, 2011 – Comments (6) | RELATED TICKERS: VRUS.DL , GSK , VRTX

Interesting article from my favorite news site, New Scientist. I post a lot of articles from there, so check back periodically or check out the site yourself.

 Article: 

Viruses might soon meet their kryptonite: an experimental drug that can, in theory, obliterate cells infected by any type of virus without harming healthy neighbours.

For 50 years, we have been fighting viruses in two ways: drugs for existing infections and vaccines to prevent infection in the first place. However, most drugs or vaccines are specific to one virus, viral strain or family of related viruses. When a virus mutates – as they so often do – researchers must retool our medicines.

The new drug targets a molecule common to all virus-infected cells. Nearly every virus generates strings of double-stranded RNA longer than 30 base pairs during transcription and replication, in an attempt to duplicate itself and commandeer its host cell's machinery. Healthy mammalian cells do not produce double-stranded RNA longer than 23 base pairs.

The immune artillery within mammalian cells includes a protein that exploits this viral characteristic. Todd Rider of the Massachusetts Institute of Technology's Lincoln Laboratory in Lexington, Massachusetts, and his colleagues combined this protein with another from the immune system to produce their new drug.

When a sentinel enzyme called protein kinase R (PKR) finds double-stranded RNA longer than 23 base pairs inside a cell, it binds to the RNA, blocks the production of viral proteins and activates the cell's defences. Many viruses, though, have evolved ways to evade PKR.

Unleash the enzymes

So Rider and his colleagues glued PKR to apoptotic protease activating factor 1 (APAF-1), a protein that triggers cell suicide by unleashing a team of destructive enzymes. Healthy cells normally reserve APAF-1 for extreme situations – to trigger self-destruction in a cancerous cell, for instance – but as part of the new antiviral drug, APAF-1 is activated as soon as PKR identifies and binds to lengthy molecules of double-stranded RNA in an infected cell.

The drug "catches the virus with its pants down", by destroying the cell before new viruses have been assembled inside it, explains Rider. Even if fragmented virus molecules escape the obliterated cell, they will be missing the protein coat that helps them to travel between cells, and so will not infect surrounding healthy tissue. Rider calls his drug double-stranded RNA (dsRNA)-activated caspase oligomeriser (DRACO).

In tests, Rider infected human and mouse cells in Petri dishes with rhinovirus, which causes some forms of the common cold in humans. DRACO prevented the virus from spreading by rapidly killing infected cells without harming healthy ones. Further tests showed that DRACO performs just as well against 14 other viruses, including the one responsible for dengue fever. It also helped boost survival rates in mice given an otherwise lethal dose of the H1N1 flu virus.

"Just as antibiotics revolutionised the treatment of bacterial infections, this project has a lot of potential to prevent or treat a whole range of infectious illnesses," says Rider. Infections on the hit list range from "the common cold to quite serious diseases – [and] even [the most] drug-resistant HIV", he says. DRACO could also act a shield against viruses that might appeal to bioterrorists, such as Ebola and smallpox.

Draconian measures

Andrea Branch of the Mount Sinai School of Medicine in New York City thinks the work is intriguing but has some reservations about its practicality. She points out that DRACO is a large protein, which may not enter cells easily.

That said, she agrees that administering DRACO early in an infection could be effective – but adds that destroying all cells infected with the virus can be dangerous in people with advanced viral infections. "Suppose 100 per cent of your hepatocytes [liver cells] are infected and you used this – you would die of liver failure."

Timothy Tellinghuisen of the Scripps Research Institute in Jupiter, Florida, adds that some viruses have evolved ways to conceal their double-stranded RNA, and so could elude DRACO. Still, "this is really an interesting paper, a very clever approach to getting rid of cells containing double-stranded RNA", he says.

Journal reference: PLoS One, DOI: 10.1371/journal.pone.0022572

6 Comments – Post Your Own

#1) On August 12, 2011 at 1:28 PM, TMFBlacknGold (99.03) wrote:

Whoops, must have forgot to copy this. Give credit where credit is due.

11:00 12 August 2011 by Ferris Jabr

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#2) On August 12, 2011 at 3:11 PM, portefeuille (99.44) wrote:

the article.

Experimental drug could defeat any virus

the paper.

Broad-Spectrum Antiviral Therapeutics

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#3) On August 12, 2011 at 3:21 PM, portefeuille (99.44) wrote:

New drug could cure nearly any viral infection

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#4) On August 15, 2011 at 3:44 PM, TMFBlacknGold (99.03) wrote:

I just researched NNVC.OB, which claims to have a similar drug in the making. This company should be a red flag to any investor, but can make some easy thumb-down points in CAPS. I set an underperform limit at $1.40 and will enjoy watching it go to zero.

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#5) On August 26, 2011 at 10:29 AM, mhy729 (34.09) wrote:

This is very interesting...not sure where I first read about it, but I'm glad to see it posted here.

That said, she agrees that administering DRACO early in an infection could be effective – but adds that destroying all cells infected with the virus can be dangerous in people with advanced viral infections. "Suppose 100 per cent of your hepatocytes [liver cells] are infected and you used this – you would die of liver failure." 

This was one of the first things that came to mind, the potential for undesirable apoptotic events.  Another even more horrific thought is the use of "apoptotic protease activating factor 1 (APAF-1)" in an engineered bioweapon, seeing as how it appears the group has been successful in stimulating the cell suicide pathway.

Nearly every virus generates strings of double-stranded RNA longer than 30 base pairs during transcription and replication, in an attempt to duplicate itself and commandeer its host cell's machinery. Healthy mammalian cells do not produce double-stranded RNA longer than 23 base pairs. 

I found this quite interesting...I believe the dsRNA of 23bp length referred to is involved in the relatively recently discovered RNAi pathway.  RNA interference itself is understood to be part of the antiviral immune response.  Excerpts from RNAi's wiki entry:

"RNA interference is a vital part of the immune response to viruses and other foreign genetic material, especially in plants where it may also prevent the self-propagation of transposons."  "The role of RNA interference in mammalian innate immunity is poorly understood, and relatively little data is available. However, the existence of viruses that encode genes able to suppress the RNAi response in mammalian cells may be evidence in favour of an RNAi-dependent mammalian immune response. However, this hypothesis of RNAi-mediated immunity in mammals has been challenged as poorly substantiated. Alternative functions for RNAi in mammalian viruses also exist, such as miRNAs expressed by the herpes virus that may act as heterochromatin organization triggers to mediate viral latency." 

Viruses are such weird things...if you read up on the techniques they've developed to overcome immune systems, you can't help but have some degree of admiration for their adaptive ability and genetic "efficiency".

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#6) On October 01, 2011 at 11:55 AM, TMFBlacknGold (99.03) wrote:

Exactly mhy729! Although you have to figure our bodies have multiple ways of fighting infection. We can make a vaccine against, at most, a family of viruses or infections, but one vaccine for all? I'm skeptical if there really is a one size fits all approach, but you can never count out science. This could lead to some interesting treatments down the road.

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