Abstract: The present disclosure provides compositions and methods for modulating PERK activity and/or expression in cells for use in treatment or prevention of viral infection, including by reducing translation of viral non-structural proteins in cells using compositions and/or compounds that inhibit PERK activity and/or expression.

Abstract: A method of identifying an antiviral agent effective against viruses, which utilize ?1 programmed ribosomal frameshifting is provided. The method includes providing cells harboring a ?1 frame plasmid including a translation start site followed by a ?1 ribosomal frameshifting signal followed by a reporter gene which is in a ?1 frame relative to the translation start site. The method further includes contacting the cells with a test agent; and measuring the activity of the reporter gene in the presence of the test agent, wherein the reporter gene activity is dependent on ?1 ribosomal frameshifting.

Abstract: The present invention provides compositions and means to identify compositions that increase ?1 PRF programmed ribosomal frameshift (?1PRF) efficiencies and/or decrease peptidyltransferase activity in a cell, and thus directly affect viral replication or assembly of viral particles. Compositions identified in accordance with the invention specifically inhibit the interaction between ribosomal protein L41 and the ribosomes thereby resulting in decreased peptidyltransferase activity of the ribosomes. Decreases in peptidyltransferase activity have been associated with increased ?1 PRF efficiencies, which in turn interfere with self assembly of ?1PRF dependent viruses thereby interfering with virus propagation. Compositions in accordance with the invention are useful as antiviral therapeutics for treating a viral infection in a patient.

Abstract: Disclosed are transgenic plants containing an exogenous nucleic acid encoding an L3 protein. The plant exhibits increased resistance to viruses and/or fungi that infect plants. The L3 proteins include wild-type proteins, spontaneously occurring mutants and non-naturally occurring L3 mutants. Also disclosed are methods of reducing the toxicity of single-chain ribosome inhibitory proteins in cells, e.g., yeast, plant and animal cells, by co-administering the L3 protein with the RIP. Further disclosed are non-naturally occurring L3 mutants that (a) substantially fail to bind single-chain RIPs that bind endogenous L3 proteins, (b) are unable to maintain M1 killer virus, (c) promote altered programmed ribosomal frameshift efficiency, (d) exhibit resistance to peptidyltransferase inhibitors, and combinations of any of (a)-(d).