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Scientists Uncover Deadly Ebola Virus's "Achilles' Heel"
Scientific American ^ | 7/10/08 | Nikhil Swaminathan

Posted on 07/11/2008 10:54:41 AM PDT by LibWhacker

Finding could lead to new therapies to thwart spread of this contagious, and mostly fatal disease

In a breakthrough that could eventually help tame one of the deadliest virsuses known to man, researchers have laid bare the key to Ebola's power: a lone protein that resides on its surface. The discovery paves the way for new treatments that target and destroy the designated culprit, rendering impotent a virus that, though rare, can kill up to 90 percent of the people it infects.

The so-called Ebola virus glycoprotein, or "spike protein," was first discovered a decade ago and has been a target for scientists attempting to design vaccines and therapies to prevent it from infecting cells. But, until now, researchers did not understand the protein's structure—and thus, the best way to attack it.

"It's the only thing that the virus puts on its surface that is absolutely critical for attaching to a host and driving into that host for infection," says Erica Ollmann Saphire, an immunologist at The Scripps Research Institute in La Jolla, Calif., and a co-author of the study appearing today in Nature.

Researchers discovered that the compound is wrapped in benign carbohydrates that mask the virus's deadliness, allowing it to elude immune system scouts. (The human immunodeficiency virus, HIV, that causes AIDS also has this trait.) The good news: the discovery could pave the way for drugs designed to see through that protective coating—and trigger the immune system to attack.

"The structure of the glycoprotein shows us the very few sites on its surface that are not cloaked by carbohydrate," Ollmann Saphire explains. "These [sites] are the chink in the armor, or the Achilles' heel, that we can target antibodies against."

"We now have a much better handle on how in the world this virus gets into cells," Ollmann Saphire says. "We also have new maps we can use to develop strategies to fight against it."

Ebola is an incurable disease that was first discovered in 1976 in western Sudan and the eastern part of the Democratic Republic of the Congo (then known as Zaire). It seems to have arisen in the rain forests of Africa and parts of the western Pacific. A person acquires the virus through contact with the bodily fluids of someone already infected. It can take from two days to three weeks for symptoms of Ebola to appear. The disease presents itself with a fever, muscle aches and a cough before progressing to severe vomiting, diarrhea and rashes, along with kidney and liver problems. Death generally occurs as the result of either one or a combination of:dehydration, massive bleeding due to leaky blood vessels, kidney and liver failure. The World Health Organization has documented 1,850 cases of Ebola (mostly in sub-Saharan Africa) since its discovery; only 600 (32 percent) of the victims survived.

Researchers made their latest finding by studying the bone marrow of a lucky survivor of a 1995 Ebola outbreak in Kikwit, a city in the southwestern part of the Democratic Republic of the Congo. They found the glycoprotein attached to an antibody (a protein unleashed by the immune system to fight viruses) in the marrow, the soft core of bones where red blood cells are manufactured.

According to Ollmann Saphire, there is a receptor located deep in the bowl-shaped structure of Ebola's glycoprotein that latches onto the surface of host cells and tricks a protein there into granting the virus entry. Once inside the cells, the fast-acting Ebola co-opts their machinery to make millions of copies of itself and floods the person's bloodstream.

Judith White, a microbiologist at the University of Virginia, says that arming researchers with the protein structure that Ollmann Saphire's group has described will allow them to "nip [the virus] in the bud," by beating down Ebola before it enters its host. (Most antivirals target viruses such as HIV after they're already inside a host cell.)

"For those of us in the trenches trying to study the virus entry, and the immune reactions to the virus, and how to prevent virus entry, and how to come up with better immune therapies," she says, "this gives us all new eyes to [solving] those problems."


TOPICS: Miscellaneous
KEYWORDS: achilles; ebola; heel; virus
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1 posted on 07/11/2008 10:54:41 AM PDT by LibWhacker
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To: LibWhacker

Our understanding of life is exploding. It’s unbelievable to me the potentials we are on the verge of.


2 posted on 07/11/2008 10:59:32 AM PDT by DManA
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To: LibWhacker

Alright! Immortality is just around the corner! Better start building colonist spaceships to clear some space...


3 posted on 07/11/2008 11:02:43 AM PDT by AbeKrieger (There is a special place in Hell for Lyndon Johnson.)
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To: LibWhacker

A BTT for some exciting news. This is just about the scariest virus out there and I do not except HIV.


4 posted on 07/11/2008 11:03:59 AM PDT by Billthedrill
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To: LibWhacker

Ebola is a serious virus but epidemics can be contained with reasonable measures of quarantine and appropriate protective gear and sanitation. Fortunately, Ebola has not invaded the homosexual community, or like HIV, we would have several million cases spread around the US in order to avoid violating the civil rights of sexual deviants.


5 posted on 07/11/2008 11:15:53 AM PDT by Neoliberalnot ((Hallmarks of Liberalism: Ingratitude and Envy))
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To: DManA
You got it. Antibody based medicine holds amazing potential.

Antibodies are formed by randomly shuffling the “highly variable” regions of the antibody DNA to make about every conceivable combination. This makes a “lock” that can fit around a very specific “key”. When in utero those antibodies circulate and any that recognize their specific “key” are destroyed because they recognized “self”. The rest are on alert looking for anything that might fit so it can trigger an immune response and massive proliferation of that particular antibody.

By isolating this “spike” that they wish to raise an immune response to, infecting a rabbit with it, then harvesting the resulting antibodies that can then be linked to medicine or may have a medicinal effect just by binding to and blocking the “spike” that the virus needs to enter the cell.

Antibody based medicines have amazing potential.

6 posted on 07/11/2008 11:21:16 AM PDT by allmendream
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To: LibWhacker

A minor point, but this sentence bothered me:

“The so-called Ebola virus glycoprotein, or ‘spike protein’ ....”

In the scientific world, “glyco” means “sugar,” and it comes from the greek word “glyco,” which means “sweet.” It’s just a bit remarkable to me that a SciAm writer and editor decided that “glycoprotein” meant “spike protein,” when it really means “sugar / protein [molecule].”


7 posted on 07/11/2008 11:23:31 AM PDT by Jubal Harshaw
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To: LibWhacker
(The human immunodeficiency virus, HIV, that causes AIDS also has this trait.)

If they already know this about HIV, where is the good news?

8 posted on 07/11/2008 11:24:30 AM PDT by donna ( I am confident that we can create a Kingdom right here on Earth. - Barack Hussein Obama)
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To: donna

As I interpret the article, the good news is the discovery of the spike protein on the virus and figuring out the protein’s structure, not the fact that the virus tries to cloak itself in carbs.


9 posted on 07/11/2008 11:39:37 AM PDT by LibWhacker
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To: Neoliberalnot

The only saving grace of Ebola is that it kills relatively quickly after infection. HIV is a different kind of danger because a carrier can have it for years without knowing. Can you imagine an Ebola with a year-long carrier stage before it kills 2/3 of the hosts?


10 posted on 07/11/2008 11:47:13 AM PDT by antiRepublicrat
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To: LibWhacker

Oh, thanks! I missed a step.


11 posted on 07/11/2008 11:47:21 AM PDT by donna ( I am confident that we can create a Kingdom right here on Earth. - Barack Hussein Obama)
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To: antiRepublicrat
"The only saving grace of Ebola"

Indeed. It's always puzzled me why a virus would kill off it's host so quickly. It's never computed for me from a survival standpoint.

12 posted on 07/11/2008 12:13:22 PM PDT by Proud_texan
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To: allmendream

Did you see this one?

http://www.freerepublic.com/focus/f-chat/2041806/posts


13 posted on 07/11/2008 12:15:16 PM PDT by DManA
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To: DManA

Yep. I posted on that thread about how a plant deals with disease (by cutting off food and water to the effected area and growing around it). ;)


14 posted on 07/11/2008 12:20:09 PM PDT by allmendream
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To: allmendream

Yea, I want back and found that. Here’s what I believe ( layman’s faith only) - for every unique life form there is a key that will kill it.


15 posted on 07/11/2008 12:31:42 PM PDT by DManA
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To: DManA
At least one. There are many thousands of genes in the human genome that if mutated so they do not function are embryonic lethal. At University a professor identified many of those lethal genes in bacteria and sold the list to a drug company as “targets of interest”. Stop any of the genes on that list from functioning = dead bacteria.
16 posted on 07/11/2008 12:40:55 PM PDT by allmendream
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To: LibWhacker

Imagine how different our culture would be if HIV killed as fast as Ebola.


17 posted on 07/11/2008 12:46:28 PM PDT by mikey_hates_everything
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To: LibWhacker
...Judith White, a microbiologist at the University of Virginia, says that arming researchers with the protein structure that Ollmann Saphire's group has described will allow them to "nip [the virus] in the bud,"...

Nip it, nip it, nip it!

18 posted on 07/11/2008 12:58:04 PM PDT by FReepaholic (Me no bottom man. Me top man.)
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To: mikey_hates_everything

Imagine how different our culture would be if HIV killed as fast as Ebola.
****************************************************
It’d be 1978 in San Francisco everywhere ,,, HIV never would have made it from Africa==>Haiti==>USA the infected people would have died (in the 1950’s??) and we would have gay rights groups marching to get organ selling/purchasing legalized (plenty of sellers in China and India) to combat Hepatitis.


19 posted on 07/11/2008 3:20:57 PM PDT by Neidermeyer
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To: antiRepublicrat

Keep in mind AIDS has killed millions while Ebola has killed less than a 1000. WE also have at least a million more cases of HIV in this country with many infected hosts continuing to spread it in largely, unfettered fashion. We have zero Ebola cases. We have spent more money prolonging the lives of HIV infected patients on a per capita patient basis than on cancer, heart disease, lung disease, diabetes, and Alzheimers combined fighting a disease easily prevented by altering behavior. Go figure.


20 posted on 07/12/2008 11:20:42 AM PDT by Neoliberalnot ((Hallmarks of Liberalism: Ingratitude and Envy))
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