Scientists at The Scripps Research Institute (TSRI) have identified weak spots on the surface of Ebola virus that are targeted by the antibodies in ZMapp, the experimental drug cocktail¹ administered to several patients during the recent Ebola outbreak. The study, led by TSRI structural² biologists Andrew Ward³ and Erica Ollmann Saphire and published online ahead of print this week by the journal Proceedings⁴ of the National Academy of Sciences, provides a revealing 3-D picture of how the ZMapp antibodies bind⁵ to Ebola virus.

 

"The structural images of Ebola virus are like enemy reconnaissance," said Saphire. "They tell us exactly where to target antibodies or drugs."

 

Ward said, "Now that we know how ZMapp targets Ebola, we can compare all newly discovered anti-Ebola antibodies as we try to formulate⁶ an even better immunotherapeutic cocktail."

 

 

ZMapp, developed by San Diego-based Mapp Biopharmaceutical, was used in August to treat several patients in the ongoing⁷ Ebola virus outbreak. Although five of the seven patients who received ZMapp survived, researchers cannot yet say for sure whether ZMapp made a difference in their recoveries.

 

The new study explains why ZMapp could have been effective. Using an imaging technique called electron microscopy, researchers found that two of the ZMapp antibodies bind near the base of virus, appearing to prevent the virus from entering cells. A third antibody binds⁸ near the top of the virus, possibly acting⁹ as a beacon¹⁰ to call the body's immune system to the site of infection.

 

The new picture of ZMapp reveals the two antibodies that bind near the base of the virus seem to be competing for the same site. While this appears to be a particularly vulnerable spot on Ebola virus's surface as identified in previous studies, one question now is whether future cocktails¹¹ should continue to use two antibodies to target this site or try to attack the virus from a third angle.

 

"This information helps guide decisions about how to formulate these life-saving therapies," said C. Daniel Murin, a graduate student in the labs of Ward and Saphire and first author of the new study. "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?"

 

Luckily, while the Ebola virus has undergone more than 300 genetic¹² changes in the current outbreak (according to research published in the journal Science in August), the new study indicates the sites where the ZMapp antibodies bind have been unaffected so far.

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