A 2-amino-1,8-napthyridine derivative that is described to bind single guanine bulges in RNA-DNA and RNA-RNA duplexes,1 was synthesized and its interaction with the single G bulge in the conserved CREX of the Hepatitis E Virus (HEV) genome was explored by NMR and molecular modeling. Results indicate that the ligand intercalates in the internal loop, though none of the expected hydrogen bonds with the single G in the bulge could be demonstrated.