Mutant Ebola Virus May Evade Drugs, Study Finds

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The Ebola virus strain that’s killed more than 8,600 people in West Africa is mutating in a way that could make experimental drugs less likely to help, researchers reported Tuesday.

They said they’d found 10 new mutations that might interfere with how three of the most advanced drugs work against Ebola. The drugs, including the experimental ZMapp given to several Ebola survivors, should be tested against the current strain, the researchers said.

“Based on our findings, the virus has changed and is continuing to change,” said Jeffrey Kugelman, a viral geneticist at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), who led the research published in the journal mBio.

All viruses mutate, some faster than others. Ebola changes slightly from outbreak to outbreak, and the more people or animals infected, the more likely the virus is to mutate as it replicates inside a living body.

"The virus has changed and is continuing to change.”

The virus that’s sickened more than 21,000 people in Liberia, Guinea and Sierra Leone is called Ebolavirus Makona variant. It’s similar to the strains that have caused outbreaks in the Democratic Republic of the Congo, formerly Zaire.

Kugelman’s team, with researchers at Harvard University and the Massachusetts Institute of Technology, compared the genetic sequence of the Ebola Makona samples to Ebola Zaire and found 600 mutations. That sounds like a lot, but may not mean much for treatment.

However, they found 10 mutations that affect the parts of the virus targeted by treatments including ZMapp, a drug made by the Canadian company Tekmira, and one called AVI-7537, being developed by Massachusetts-based Sarepta Therapeutics.

All these drugs are specifically designed to attack Ebola based on its physical structure. ZMapp, made by San Diego-based Mapp Biotherapeutics, consists of three genetically engineered immune system proteins called monoclonal antibodies. They are designed to recognize and neutralize Ebola.

“Their efficacy should be reevaluated against the currently circulating strain."

The Tekmira and Sarepta drugs are based on an approach called antisense. They’re designed to interfere with the virus by sticking to it and stopping it from infecting cells.

The mutations affect the bits of the virus that these three drugs are specifically designed to interfere with or recognize, Kugelman’s team said.

“Their efficacy should be reevaluated against the currently circulating strain,” they suggested. Tekmira has made some adjustments, it says in company statement, but hasn't yet tested them.

The World Health Organization has approved the use of experimental therapies to fight the Ebola epidemic. ZMapp has done well in monkeys, but they were not infected with Ebola Makona. And while most of the human patients given ZMapp survived, not all have, and doctors stress they have no idea if the drug has actually helped anyone.

The same is true of Tekmira's drug.