Combination Treatment Highlights Ebola's Weak Spots

ZMapp, an experimental antibiotic, pinpointed weak spots on the Ebola virus (EBOV)’s surface, scientists at The Scripps Research Institute (TSRI) discovered.

Two candidate monoclonal antibody (mAb) cocktails, MB-003 and ZMAb, had shown promising results against the EBOV. Based on their success, they had been formed into combination treatment called ZMapp, which will go into clinical trials in 2015, a TSRI statement mentioned.

A newly published study in Proceedings of the National Academy of Sciences (PNAS) provided a 3-dimensional explanation of how the drug binds to vulnerable locations on the virus.

“The structural images of Ebola virus are like enemy reconnaissance,” lead author Erica Ollmann Saphire, a TSRI structural biologist, said. “They tell us exactly where to target antibodies or drugs.”

While ZMapp was used on 7 Ebola patients in August, how the drug led to the survival of 5 of those patients could not be tied to the drug prior to the study, TSRI also reported.

Using electron microscopy, investigators witnessed 2 of ZMapp’s antibodies competed at attacking the same location at the virus’ base. As a result, EBOV is unable to infect cells. A third antibody attaches to the top of the EBOV, alerting the immune system of the location and existence of a threat.

While their study has highlighted EBOVs’ weak spots, C. Daniel Murin, a graduate student in the labs of Andrew Ward and Sapphire and first author of the study, claimed using an additional agent to attack the EBOV from a third angle is still in question.

“Going forward, this work now provides a basis for strategic selection of next-generation antibody cocktails against Ebola and related viruses and a model for predicting the impact of ZMapp on potential escape mutations in ongoing or future Ebola outbreaks,” the scientists concluded.