EBOLA'S WEAPON: Researchers have determined the structure of the protein that kicks off the process by which Ebola infects cells.
Image: C. Corbaci and E. Ollmann Saphire
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In a breakthrough that could eventually help tame one of the deadliest viruses 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."
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13 Comments
Add CommentYeah, they've had this big discovery...but you still haven't told us HOW they did it. Did a new machine allow them to figure it out? Did a new member show up with a new idea? HOW/WHY did the discover happen NOW? Why not last year? There's a HOLE in your report. Patch it please!
Reply | Report Abuse | Link to thiswait.....(top) though rare, can kill up to 90 percent of the people it infects. (bottom) since its discovery; only 600 (32 percent) of the victims survived. OK i have now ignored the rest of the article.
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Reply | Report Abuse | Link to thisThe different percentages are based on the fact that there are different strains of ebola, each with different virulences. For instance, the worst, ebola Zaire, is the most deadly, averaging something like 90% fatality and in one outbreak killing 100% of people who got it (hence the comment can kill up to 90% of people it infects). On the other hand, other strains (Sudan and Ivory Coast, maybe Uganda) are less deadly (the only statistic I could find put Sudan at 54% fatality) and one strain, ebola Reston, doesn't infect people at all, just monkeys. Thus, the average of all the strains is apparently only 68% fatality, but that doesn't mean that any one strain is 68% fatal.
OK.... Lets take a look at this. If it is true that in an out break it killed %100 of the people that got it. Then it "could" kill up to 100% of of the infected people. Thus the article is still inaccurate.
Reply | Report Abuse | Link to thisYet the Africans refuse to take charge of their destiny, they refuse to investigate what kills them expecting the Americans to do it, as if there is Ebola in America, they always want somebody else to do it, The black should be free in Africa, where else can they be free, a free Africa would have found a cure for Ebola by now.
Reply | Report Abuse | Link to thisThe "gap" in the article about how this information was determined is good scientific research techniques found in genetic research circles around the world. Including the details in this article would make the article volumes in size. I suggest that you look up genetic research/how proteins work on another site to fill in your "gap". I understood the article just fine.
Reply | Report Abuse | Link to thisall the scientific details on how they solved the structure is in their publication in Nature under the Material and Methods section. most of their techniques used are standard in the structural biology field. This is a very difficult structure to solve given it's inherent flexibility so this is probably the main reason why it has taken so long to solve.
Reply | Report Abuse | Link to thisMost of the details of how they solved the structure is published in their paper in Nature under the Material and Methods section. This is a very difficult structure to solve given its inherent flexibility, this is why it has taken so long. I'm sure it was a lot of hard work for the authors.
Reply | Report Abuse | Link to thisWhat has this racist rant got to do with medical research?
Reply | Report Abuse | Link to thisMy fave part there is glycoprotein. And how does Ebola virus's receptors stick/attach to an antibody?
Reply | Report Abuse | Link to thisMy fave part there is glycoprotein. And how does Ebola virus's receptors stick/attach to antibodies?
Reply | Report Abuse | Link to thisif you click on the link to the actual scientific article, you will be able to know how they did it. It wasn't done last year or any other year because of obvious reasons...there were lots of technical difficulties in achieving a scientific feat such as this one.
Reply | Report Abuse | Link to thisthis is freaky article, and yes please include hwo was the discovery of the clues to defeat this virus
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