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Research Reveals Ebola’s Enzymes

Discovery may eventually lead to therapy for treating virus

By Nicholas J. Melvoin, CONTRIBUTING WRITER

Three Harvard Medical School researchers are among a group that released a study last week identifying key enzymes that cause the deadly Ebola virus—findings that may eventually lead to an antiviral therapy that could be effective in treating the Ebola virus and others like it.

Associate Professor of Medicine James M. Cunningham and Research Fellow in Medicine Kartik Chandran were the principal authors of the study, which was published in Science Express on April 14. The two authors have been collaborating on the effort for almost two years, according to Chandran.

Assistant Professor of Microbiology and Molecular Genetics Sean Whelan was also one of the five authors.

Their study identified cellular enzymes that the Ebola virus needs to reproduce. When these enzymes are blocked, the virus loses most of its ability to infect, according to a news release from the National Institutes of Health.

Cunningham’s interest in the virus evolved from his, and the other researchers’, interest in how retroviruses infect cells, he wrote in an e-mail.

“From these studies, we noted some intriguing similarities with reported properties of Ebola virus that gave us clues into how Ebola might invade cells,” Cunningham wrote.

The research was conducted at the United States Army Medical Research Institute of Infectious Diseases at Fort Detrick in Maryland.

Because of the highly hazardous nature of the virus, it took the researchers a year to set up the system in which the virus would be studied. But once the research began, the testing went relatively quickly, according to Chandran, who attributed this in part to his experience in working with similar types of enzymes.

While the study made great strides in understanding the Ebola virus, there is still much work to be done, according to both Cunningham and Chandran.

“Our goal is to use this information to understand in more detail the molecular mechanism by which Ebola virus uses cell surface enzymes to invade cells,” Cunningham wrote.

Chandran noted that the next step will be to look at other cell types and the effect of their research on animals. Chandran said that the study’s authors are also interested in the effects of their research on similar viruses, such as the Marburg virus, which is currently sweeping through parts of Africa.

But despite future challenges, the researchers said they are eager to forge ahead.

“We now have an opportunity to pursue a therapeutic strategy,” Chandran said. “But it’s very early on. A lot more things have to happen before one could say that there’s a therapy for the Ebola virus.”

“It is premature to think about using the inhibitors as anti-Ebola drugs until these studies are completed,” Cunningham wrote.

The two professors collaborated on the project with Nancy J. Sullivan of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases and Ute Felbor, a former Harvard post-doctoral fellow and a current assistant professor in Germany.

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