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Bacterial protein synthesis is the target for several classes of established antibiotics. This report describes the characterization of a novel translation inhibitor produced by the soil bacterium Flexibacter. The dipeptide antibiotic TAN1057 A/B was synthesized and designated GS7128. As reported previously, TAN1057 inhibits protein synthesis in both Escherichia coli and Staphylococcus aureus, leaving transcription unaffected. Cell-free translation systems from E. coli were used to further dissect the mechanism of translational inhibition. Binding of mRNA to ribosomes was unaffected by the drug, whereas the initiation reaction was reduced. Elongation of translation was completely inhibited by GS7128. Detailed analysis showed that the peptidyl transferase reaction was strongly inhibited, whereas tRNA binding to both A- and P-site was unaffected. Selection and analysis of drug-resistant mutants of S. aureus suggests that drug uptake may be mediated by a dipeptide transport mechanism.

Ribavirin, in combination with interferons, has proved clinically useful for the treatment of hepatitis C virus (HCV) infection despite uncertainty as to its true mechanism of action. Its immunomodulatory effects have been proposed to be crucial for its efficacy in HCV treatment. Two new derivatives of zibavirin, Levovirin and virmidine, are currently in development as HCV therapeutics. Both drugs retain ribavirin's immunomodulatory properties but appear to be less toxic than the parent drug. Clinical evaluation of these drugs may aid in understanding the relevant mechanism of action of ribavirin itself, as well as the role of immunomodulators in HCV therapy.