NIH R01 · 2024
Evolving understanding of HIV-1 reverse transcriptase structure, function, and inhibition.
During the first 30 years of this grant, using X-ray crystallography, we have been able to describe the detailed molecular architecture of HIV-1 reverse transcriptase (RT) in complex with dsDNA, RNA/DNA, and dsRNA. These include structures poised for nucleotide incorporation, catalytic complexes, and post-incorporation structures prior to translocation. All of them represent key states for understanding the comprehensive nature of reverse transcription during HIV infection, and the mechanisms of action of and resistance to nucleoside RT inhibitor (NRTI) drugs. In a collaborative effort, our crystallographic structures enabled the discovery of two non-nucleoside RT (NNRTI) drugs (rilpivirine…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.