LOS ANGELES: A new study focused on discovering the mechanism by which the lethal Ebola virus infects cells may provide vital information on how drugs can be used to fight the disease, researchers said on Thursday.

The highly contagious and, thus far, incurable Ebola virus is believed to originate in apes. Once passed to a human carrier, the virus causes massive hemorrhaging resulting in an excruciating and bloody death.

The ease of transmission of the disease has been a particular cause of concern for experts who fear that, should the virus turn up in an urban environment - either naturally or through bio-terrorism - the death toll could be huge.

Like the Marburg virus now alarming Angola, Ebola belongs to a family of viruses called filovirus. Although Ebola is comparatively rare, annually filoviruses kill thousands across Africa. However, the molecular mechanisms the Ebola virus employs to enter host cells and initiate infection are poorly understood, said US National Institutes of Health (NIH) that sponsored the study.

The researchers, whose paper is published in the latest online issue of the journal Science, identified two cellular enzymes Ebola virus must have to produce to infect cells. When those enzymes are blocked, the virus loses most of its infectivity.

Ebola virus co-opts and uses these two enzymes to cut up one of the virus' surface proteins. Once this protein is snipped apart, the virus is free to begin multiplying, according to James Cunningham, senior author of the paper from Harvard Medical School.

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.

Reproduction of the virus in laboratory-grown cells is severely hampered by enzyme-inhibiting chemicals, and these chemicals deserve further study as possible treatments for virus infections in humans, the researchers said.

Inhibitors of cathepsins are already under clinical development as anti-cancer drugs. The authors 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."

"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," NIH Director Elias A. Zerhouni said in a statement.

"This new research sheds light on the mechanism Ebola virus uses to enter cells," noted Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID), which is a component of the NIH.

"These findings raise the possibility of a broad-spectrum antiviral therapy that could be effective against multiple hemorrhagic fever viruses."

(China Daily 04/16/2005 page8)