"This new research sheds light on the mechanism Ebola virus uses to enter cells," said National Institute of Allergy and Infectious Diseases (NIAID) director Anthony Fauci. "These findings raise the possibility of a broad-spectrum antiviral therapy that could be effective against multiple hemorrhagic fever viruses."
The researchers identified two cellular enzymes Ebola virus must have to reproduce. When those enzymes are blocked, the virus loses most of its infectivity.
The Ebola virus co-opts and uses these two cellular enzymes to cut up one of the virus' surface proteins. Once this protein is snipped apart, the virus is free to begin multiplying. The scientists applied broad-spectrum enzyme inhibitors to mammalian cells before exposing them to Ebola virus.
When one specific cellular enzyme, cathepsin B, was inhibited, the infectivity of Ebola virus dropped to near zero. An accessory role is played by another cellular enzyme, cathepsin L, the scientists determined.
Ebola virus, like the Marburg virus now alarming Angola, is a filovirus, a family of viruses that cause severe and frequently fatal hemorrhagic fevers. "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," said (NIH) director Elias Zerhouni.
Inhibitors of cathepsins are already under clinical development as anti-cancer drugs. The author, James Cunningham of the Harvard Medical School in Boston wrote: "Further investigation of the antiviral efficacy of [enzyme] inhibitors may…be warranted."
"The wealth of existing knowledge regarding the design and in vivo pharmacology of these inhibitors may facilitate development of an anti-Ebola-virus therapy."
Ebola, first identified in 1976, causes severe internal bleeding. Last year an outbreak of Ebola killed more than 120 people in the Congo Republic and also killed many gorillas living in a nearby wildlife preserve.
Normally, antigen-capture enzyme-linked immunosorbent assay (ELISA) testing, IgM ELISA, polymerase chain reaction (PCR), and virus isolation can be used to diagnose a case of Ebola HF within a few days of the onset of symptoms.
Persons tested later in the course of the disease or after recovery can be tested for IgM and IgG antibodies; the disease can also be diagnosed retrospectively in deceased patients by using immunohistochemistry testing, virus isolation, or PCR.
The latest study is published online in Science Express (April 14).