NIGMS support for AIDS research focuses on the basic structural, biophysical and cell biological investigation of HIV and its interaction with the host cell. While one goal is to advance fundamental knowledge, NIGMS’ specific interest in funding these studies is to contribute to defining new targets for antiviral therapeutics.
For more than 25 years, NIGMS has funded research leading to a greater understanding of the structures and functions of the HIV enzymes and virion components . Research includes high-resolution structural determination of viral enzymes, detailed analyses of resistance to current therapeutics and computational and in silico design of, or screening for, new HIV replication inhibitors. Results have contributed in large measure to the development of drugs that target both reverse transcriptase and the viral protease, yielding greatly improved outcomes and quality of life for people with HIV.
Five NIGMS-funded Specialized Centers for HIV/AIDS-Related Structural Biology, which are co-funded by NIH's National Institute of Allergy and Infectious Diseases, focus on the components of the HIV infected cell that are critical to the viral life cycle. Elements of the host cell are not subject to the virus' rapid evolution and thus represent more stable targets for therapeutic development.
In addition, NIGMS supports fundamental studies on the biology and biochemistry of HIV proteins and nucleic acids and their interactions with the host cell. Diverse areas of research include enzymology of HIV proteins, analysis of how HIV proteins commandeer essential cellular machinery and proteomic investigations to identify key nodes of interaction.
NIGMS supports both research and training grants involved in AIDS-related research through a variety of mechanisms: investigator-initiated research (R01) and program projects (P01), centers (P50), and T32 and F32 training and fellowship grants. The majority of these are administered through the Division of Cell Biology and Biophysics (CBB) with funding supplied to NIGMS through the NIH Office of AIDS Research. The program is managed within CBB by Michael Sakalian, Ph.D. NIGMS also sponsors an AIDS-Related Structural Biology Meeting held on the NIH Campus in Bethesda, Maryland.
The five specialized centers will continue to focus on elucidating the three-dimensional structures of challenging HIV-related targets, but also will use a variety of complementary techniques to gain a mechanistic understanding of key events in the HIV infectious cycle and advance understanding of HIV replication. For example, new single molecule analysis methods hold the promise for a dynamic understanding of HIV-host complexes. The short-term impact of studies like these will be an understanding of viral replication and host interaction in unprecedented detail. Over the long term, the studies will inform the design of new therapeutics for HIV and may offer a new paradigm for antiviral therapeutic design.
NIGMS also continues to support AIDS-related structural biology research in response to the standard R01 (PA-16-160) and P01 program project (PAR-16-433) solicitations.