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ZMapp analysis could improve effectiveness of Ebola treatments
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Analysis of the experimental drug cocktail ZMapp’s effect on Ebola virus may lead to more effective versions of the treatment, according to recent data.
Researchers from The Scripps Research Institute (TSRI) examined single-particle electron microscopy reconstructions of the monoclonal antibodies in the immunotherapeutic cocktail, as well as those from the MB-003 and ZMAb treatments used to create it. When introduced to Ebola virus, they were able to observe the antibodies’ activity.
“The structural images of Ebola virus are like enemy reconnaissance,” Erica Ollmann Saphire, PhD, structural biologist at TSRI, said in a press release. “They tell us exactly where to target antibodies or drugs.”
The researchers found that two of ZMapp’s antibodies recognize overlapping epitopes. While this weak spot near the base of the virus is a clear target for the antibodies, it appears that the two compete as they attempt to bind. This may weaken the cocktail’s efficacy, the researchers wrote.
“This information helps guide decisions about how to formulate these lifesaving therapies,” C. Daniel Murin, graduate student at TSRI, said in the release. “Instead of including two different antibodies that do the same thing, why not use twice as much of the more effective one instead? Or include a third antibody against a different site to stop the virus a third way?”
A third antibody able to bind near the top of the virus was identified as well, and is believed to serve as a beacon to call the body’s immune system to the virus.
“Now that we know how ZMapp targets Ebola we can compare all newly discovered anti-Ebola antibodies as we try to formulate an even better immunotherapeutic cocktail,” Andrew B. Ward, PhD, structural biologist at TSRI, said in the press release.
ZMapp has been given compassionately to seven patients infected during the recent Ebola outbreak, but lacks conclusive data. The treatment is expected to begin clinical trials in 2015.
Disclosure: The researchers report no relevant financial disclosures.
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