Researchers Discover Important Structure for Drug Development

St. Jude Children's Research Hospital (ALSAC)
Wednesday, 1 November 2000

Results Impact Both Children and Adults with Common Respiratory Virus

(Memphis, Tennessee, November 1, 2000) Researchers at St. Jude Children's Research Hospital®, in collaboration with scientists at the University of St. Andrews, Fife, Scotland, have discovered the structure of a critically important protein, the hemagglutinin-neuraminidase (HN), for Newcastle disease virus - part of the family of paramyxoviruses that includes the parainfluenza viruses (hPIV-1, hPIV-2, hPIV-3, and hPIV-4). This family of viruses is responsible for illnesses such as croup, bronchitis, bronciolitis and pneumonia. Parainfluenza (both hPIV-1 and hPIV-3) is the second most common viral infection in children under five years of age. Ninety-five percent of all children will show positive antibodies of parainfluenza virus, meaning they have been infected in the past. Parainfluenza may occur anytime of the year and can be especially dangerous for children suffering from chronic illnesses or who have a compromised immune system.

In the November issue of the journal Nature Structural Biology, St. Jude researcher Allen Portner, Ph.D., and his colleague Gary Taylor, Ph.D., University of St. Andrews, report that they were able to create a three-dimensional structure of the HN molecule in the Newcastle disease virus. They discovered that both the binding, or hemagglutinin, and the releasing, or neuraminidase, activities were located at the same place in this structure.

"Now, it will be possible to design a drug that will fit into that site because the drug will look like the natural molecule that the virus is looking for in order to bind with it," Dr. Portner said. "Therefore it will both stop the virus from attaching to the target cell in the throat, and it will stop the neuraminidase activity, or prevent the virus from releasing from infected cells that could go on to infect new cells. These findings provide the opportunity to design a drug that will fit into that site and thereby interrupt the infectious process by preventing virus attachment, entry, and release from target cells of the respiratory tract."

The research on Newcastle disease virus also has implications for adults. The two other forms of parainfluenza virus, hPIV-2 and hPIV-4, strike mostly adults, but these findings, and the promise of a vaccine, will work the same for these subtypes.

St. Jude Children's Research Hospital, in Memphis, Tennessee, was founded by the late Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is supported through the funds raised by the American Lebanese Associated Charities® (ALSAC)®. All St. Jude patients are treated regardless of their ability to pay. ALSAC covers all costs of treatment beyond those reimbursed by third party insurers, and total costs for families who have no insurance.

For more information, or to contact St. Jude Children's Research Hospital (ALSAC), see their website at: www.stjude.org