Enzyme found to disrupt Ebola replication

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Apr 15, 2005 (CIDRAP News) – The Ebola virus has yielded an important behavioral clue that could lead to a treatment for the incurable infection that kills 50% to 90% of its victims, researchers have announced.

Enzyme-inhibiting chemicals have stalled the virus' reproduction in laboratory-grown cells, reports senior author James M. Cunningham, MD, of Brigham and Women's Hospital and Harvard Medical School in Boston, in an article published online yesterday in Science. The research was partly supported by the National Institute of Allergy and Infectiuos Diseases (NIAID), part of the National Institutes of Health (NIH).

The researchers found two cellular enzymes the Ebola virus depends upon to reproduce. When they are blocked, the virus' infectivity drops a great deal, according to a news release from NIAID.

The Ebola virus uses the cellular enzymes to cut up viral surface proteins. Once the protein is split, the virus can multiply.

Scientists applied broad-spectrum enzyme inhibitors to mammal cells before exposing them to Ebola. When an enzyme called cathepsin B was suppressed, the infectivity of the Ebola virus "dropped to near zero," the news release said.

The other enzyme, cathepsin L, played a helping role in Ebola multiplication, researchers found. Drugs that inhibit cathepsins are already being developed to fight cancer.

The findings may be significant because Ebola, like its fellow filovirus Marburg, is part of a family of viruses that strike relatively rarely but can cause severe, often fatal hemorrhagic fevers. An ongoing Marburg outbreak in the Uige province of Angola had as of yesterday sickened 235 people, killing 215.

"Finding medical countermeasures for viral hemorrhagic fevers is a global public health priority because not only do these diseases occur naturally, but they also have the potential to be unleashed by bioterrorists," says NIH Director Elias A. Zerhouni, MD.

The research illuminates the mechanism the Ebola virus uses to insinuate itself into cells, said NIAID Director Anthony S. Fauci, MD. "These findings raise the possibility of a broad-spectrum antiviral therapy that could be effective against multiple hemorrhagic fever viruses.

Chandran K, Sullivan NJ, Felbor U, et al. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science 2005 (published online Apr 14) http://www.sciencemag.org/cgi/content/abstract/1110656v1

See also:

NIH news release at http://www.nih.gov/news/pr/apr2005/niaid-14.htm.

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