Novel Antivirals Based on 2-Deoxystreptamine

We will develop a small molecule, orally active antiviral agents designed to halt replication of ththe level of transcription by inhibiting the Rev protein/RRE interaction. This protein/nucleic acidviral replication.(1-3) Zapp and coworkers demonstrated for the first time that a small molecule amineomycin B, could disrupt the Rev/RRE interaction.(4) The aminoglycoside antibiotics however possessbioavailability, and binding site selectivity profiles that require improvement.(5-9) In an effort twould like to step away from the aminoglycoside antibiotic skeleton and yet have our compounds retaithe parent molecule. We will use as our central building block 2-deoxystreptamine, the same aminocycvirtually all of the naturally occurring aminoglycoside antibiotics. Derivatization of 2-deoxystreptcarbohydrate moieties, whose functional groups are in accord with our proprietary structure activityafford neomycin B mimics that display the desired inhibitory properties while having improved therapDetermination of compound efficacy is performed in house using cell-based and multiple in vitro assa