Abstract: A defined target for hepatitis and picornaviruses, and other viruses which utilize binding of the ribosomes to the internal ribosome entry site (“IRES”) of eukaryotic cells for viral protein translation, has been identified. Useful anti-viral compositions are compounds which block binding, physically or sterically, of the eukaryotic ribosome to the IRES to prevent translation of the viral proteins. The inhibitory molecule may bind to any ribosome subunit, initiation factor, or exposed site on the 40 S, 60 S, 48 S complex or 80 S complex in order to alter specificity of binding of the ribosome. The compounds are identified using the screening methods described herein from libraries of known compounds, including antibiotics. These compounds are then formulated for administration to a patient infected with or exposed to the virus.