New findings on HIV can help validate structure-based drug design approach

The development of new drugs to treat and prevent HIV/AIDS depends on understanding the basic biology of how the virus infects human cells. For 25 years, researchers supported primarily by NIH's National Institute of General Medical Sciences (NIGMS) have been generating the structures of key viral proteins, revealing important insights into the virus's mechanisms and, more importantly, its Achilles' heels.

This NIGMS program is one element of NIH's broader HIV/AIDS research effort.

Initially, the program's main objectives were to determine the structures of virally encoded molecules and to test the relatively new idea that such structural knowledge could be used to design new drugs. The 30 research groups involved in the effort were highly successful. They revealed new insights into how viral proteins function during the infectious cycle and how the virus can develop drug resistance. The work also helped to validate the structure-based drug design approach. An important example is Viracept (nelfinavir), which is widely used to inhibit the action of the viral protein HIV protease and, as a result, stop the virus from infecting more cells.

Now, the program centers on a new challenge: detailing HIV-host events during all stages of the virus's life cycle. The mission, which pushes the state of the art in structural biology and HIV research, is to visualize how the different components interact and point to new approaches for disrupting those interactions.

Specific areas of interest include:

•Identifying HIV-host protein interactions most essential to the virus's life cycle;

•Structurally understanding how viral proteins seize and then use the host's cellular machinery;

•Discovering cellular proteins and biochemical pathways that enable certain cell types to resist infection by HIV; and

•Developing methods that combine multiple molecular imaging techniques, overcoming limitations of the individual techniques.

Researchers will discuss the exciting progress in these and related areas during the 25th annual meeting on HIV/AIDS-related structural biology. The meeting, which is free to attend, will be held on the NIH campus in Bethesda, Md., from March 28 to March 30, 2011.