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In normal cases, the virus gets into the host cell through the endosome, a small compartment that is separated from the rest of the cell by a membrane. Inside the endosome, a glycoprotein on the virus’s surface receives a signal from the host cell to merge, and deploys loop-shaped structures that shoot from the surface of the virus. Think of them like harpoons, said study co-leader Kartik Chandran, a professor of microbiology and immunology at the Albert Einstein College of Medicine. Known as fusion loops, they latch onto the host cell’s membrane and pull it close enough to the virus so that it can fuse with the cell.
At that point, it’s game over. Once the virus fuses into the rest of the cell and replicates, it can start spreading the infection to the rest of the body.
The antibodies discovered by the researchers disrupt this process. Antibodies are proteins that float around in the blood stream in search of a specific virus that they target. In the case of Ebola, the antibodies “hitchhike” with the virus into the cell, explained Dye, and then bind with the glycoprotein, leaving the fusion loops unable to deploy. This makes the virus incapable of replicating and spreading the infection.
Each strain of ebolavirus has its own glycoprotein, but remarkably, these two antibodies can bind to all of them. Dye said that they “have an amazing potential to thwart any ebolavirus.”
The first time they saw the antibodies neutralize all five of the viruses “was pretty incredible,” said Zachary Bornholdt, director of antibody discovery at Mapp Biopharmaceutical and another co-lead on the study.
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The research team hopes that these antibodies will be able to fight ebolaviruses that have not yet been discovered. The fifth known ebolavirus, called Bundibugyo, was identified only in 2007.
“We don’t know what’s going to come out of the woods next,” Dye said.
But given that these antibodies appear to work against all current ebolaviruses, it is likely they will be able to work against future strains as well.
This discovery could lead to several different types of treatments, including a vaccine. It could also help create a powerful prophylactic treatment that could be given to people who may have been exposed to the virus.
“If you give the antibodies a head start,” Chandran said, “the virus is toast.”
The team has already moved into primate trials, and are collaborating with another group of Ebola researchers that also published a paper this week about Ebola antibodies, though theirs were found in monkeys.
Dye estimated that there could be a human trial with these antibodies in as little as two to three years, depending on when the next outbreak is. The interaction between antibodies and glycoproteins could also be studied to develop treatments for other viral illnesses, he said, such as Dengue fever and HIV.
Current studies are encouraging, said Chandran. “We’re very optimistic.”
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