NCI Basic Research into HIV Structure Pays Off in AIDS Drug Development

BETHESDA, Md--NCI research from the 1980s, in which scientistsused crystallography to study the structure of the human immunodeficiencyvirus (HIV), paved the way for development of the current cropof HIV-specific protease inhibitors (see " Early CombinationTreatment May Provide HIV Control" for a report on clinicaltrials of protease inhibitors).

Data from crystallization studies were used to develop 3-dimensionalmodels of the enzyme. Researchers were then able to determinethe shape a protease inhibitor must have to "fit" intothe enzyme's active site and inhibit its function.

The coordinates for the 3-dimensional image were deposited inthe Brook-haven National Laboratory database, making the structureavailable to pharmaceutical companies, who then put their drugdesign teams to work to develop novel inhibitors.

George VandeWoude, PhD, special advisor to the director of NCI'sDivision of Basic Sciences, said that the achievement "emphasizesthat basic research is worth the effort."