Federal Grant Award Summary

Rutgers The State University of New Jersey (RBHS-School of Nursing) received a $235,500 Project Grant from the National Institute of Allergy and Infectious Diseases under the Allergy and Infectious Diseases Research program (CFDA 93.855), awarded June 17, 2026, with a completion date of May 31, 2028. This R21 grant supports the structure-based development of nucleotide-competing inhibitors (NCIs) targeting HIV-1 and LINE-1 reverse transcriptases. The research aims to establish proof-of-concept for an alternative mechanism to existing nucleoside inhibitors by leveraging structural insights into how NCIs block polymerase active sites without requiring incorporation into nucleic acids.

The project deliverables encompass three integrated research aims: (1) discovery and structural optimization of NCIs targeting HIV-1 reverse transcriptase through binding module analysis and co-crystal structure determination; (2) evaluation of NCI mechanism translation to LINE-1 reverse transcriptase via structural analysis, enzymatic inhibition testing, and artificial intelligence-based structure prediction and generative design to identify LINE-1-specific candidates; and (3) development of a fragment library tailored to protein-nucleic acid interfaces for fragment screening applications. The research will generate co-crystal structures, biochemical activity data, cellular retrotransposition assay results, and computational design outputs to advance therapeutic development against both HIV-1 and emerging targets in cancer and autoimmunity.