Dr. Francesc Xavier Ruiz has received a two-year NIH R21 award from the National Institute of Allergy and Infectious Diseases (NIAID) to develop a new class of reverse transcriptase inhibitors that blocks enzyme activity through a mechanism distinct from current therapies. Dr. Ruiz is a Research Associate Professor in CABM and the Rutgers University Department of Chemistry and Chemical Biology.
Reverse transcriptase (RT) is essential for HIV replication and is also encoded by the human retrotransposon LINE-1, whose aberrant activity has been implicated in cancer, aging, and autoimmune diseases. Although existing drugs successfully target HIV RT, they primarily act as nucleoside analogs and remain limited by toxicity, drug resistance, and other pharmacological challenges. No non-nucleoside inhibitors have yet been developed against LINE-1 RT.
Building on his previous structural studies of HIV-1 RT in the laboratory of Prof. Eddy Arnold, Dr. Ruiz will investigate nucleotide-competing inhibitors, a mechanistically distinct class of compounds that bind the RT active site without being incorporated into DNA. The project will combine structural biology, biochemistry, fragment-based drug discovery, and artificial intelligence to define the molecular principles governing nucleotide-competing inhibitor recognition and to extend these principles toward discovery of inhibitors against LINE-1 RT.
The work is expected to provide new insights into reverse transcriptase inhibition, identify novel inhibitor scaffolds, and establish a foundation for future therapeutic development against HIV infection and LINE-1-associated diseases, including cancer and age-related disorders.