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Two new studies by scientists at Scripps Research show that human and mouse antibodies can bind to Ebola virus and stop infection, the research suggests antibodies like these could be key ingredients in versatile lifesaving therapeutics capable of neutralizing all members of the Ebolavirus genus.
Different viruses in the Ebolavirus genus vary in their structure, but have the same outbreak potential. Ebola virus contains fine pathogen; members of the genus Ebolavirus include Ebola virus, Sudan virus, Bundibugyo virus, Taï Forest virus and Reston virus. Each of these viruses is up to 50 percent different in amino acid sequence, making it tough to develop broad treatment strategies.
Sudan and Bundibugyo viruses were responsible for 40 percent of Ebola cases before 2013, yet current experimental Ebola therapies can’t neutralize them. All members of the Ebolavirus genus could mutate to escape immune system defenses and fight off drug therapies. The new research shows that antibodies that bind to a site on the viral “fusion loop” can neutralize all known ebolaviruses.
The fusion loop is part of the machinery that the virus uses to fuse with human cells and initiate infection. Targeting this peptide could present an opportunity to develop a universal therapy for infections caused by all five members of the Ebolavirus genus. Researchers focused on human antibody-ADI-15878. This antibody was found in the blood of an Ebola virus survivor and is the only human antibody ever found to neutralize all five members of the Ebolavirus genus.
Using a high-resolution structural technique- X-ray crystallography, the scientists modeled the interaction between the antibody and the viral glycoprotein (the protein that enables the virus to infect a cell). Ebola’s glycoprotein is covered with sugars that mask the virus from detection by the body’s immune system.
Researchers observed that ADI-15878 binds directly to one of these sugars alongside a paddle-like structure on the fusion loop. Part of the antibody then dips down and binds into a pocket that is hidden by another part of the viral glycoprotein.
For therapeutics to include antibodies that work like ADI-15878. Researchers working on Ebola vaccines could also design molecules that look like this region of the fusion loop. These molecules, called immunogens, teach the human immune system which piece of the virus to target.