Structural modeling at Scripps points to better Ebola drug cocktails

3-D model of antibodies on the ebolavirus--Courtesy of Scripps

Antivirals sometimes rely on a cocktail recipe, using a mix of antibodies to mount a multipronged attack aimed at threatening viruses. One of the drug cocktails now in preclinical development for Ebola, ZMapp--which has been used for a small group of emergency cases--was developed by San Diego-based biotech Mapp Biopharmaceutical. And now two Scripps investigators have come up with a 3-D model to show where its three antibodies stick to the virus, pointing to new and better therapies as well as informing work on other such cocktail therapies.

"The structural images of Ebola virus are like enemy reconnaissance," said Scripps' Erica Ollmann Saphire in a statement. "They tell us exactly where to target antibodies or drugs."

In ZMapp's case, Saphire notes that two of the antibodies attach to the base of the virus, which could explain why it prevents the virus from entering a cell. A third antibody plugs to the top of the virus, which may act as a beacon to the immune system.

Saphire and her colleague, Andrew Ward, add that 5 of 7 infected patients treated with the cocktail have survived the lethal virus, but no one is jumping to any conclusions about this treatment. The cocktail is slated for actual clinical trials, which are being rushed forward now as health officials around the world scramble to stem the worst outbreak of Ebola recorded since the virus was discovered in 1976.

Erica Ollmann Saphire

Some other lessons learned at Scripps: Ebolavirus is known for undergoing frequent mutations, but the ZMapp antibodies attach in apparently stable areas, which would speak to their durability as a treatment.

Their work at Scripps, though, was about more than demonstrating how the cocktail works. The investigators want to see if there are better cocktails that can do a better job. Two of the antibodies, they note, may compete at doing the same thing, making it logical to try different recipes that target other regions, which might be more effective than what ZMapp has on hand. And it could also apply to other cocktails used to fight back against damaging viruses, now and in the future.

- here's the release from Scripps

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