Peptidyl-transferase inhibitors have antiviral properties by altering programmed -1 ribosomal frameshifting efficiencies: development of model systems.
The effects of two peptidyl-transferase inhibitors, anisomycin and sparsomycin, on ribosomal frameshifting efficiencies and the propagation of yeast double-stranded RNA viruses were examined. At sublethal doses in yeast cells these drugs specifically alter the efficiency of -1, but not of +1, ribosomal frameshifting. These compounds promote loss of the yeast L-A double-stranded RNA virus, which uses a programmed -1 ribosomal frameshift to produce its Gag-Pol fusion protein. Both of these drugs also change the efficiency of -1 ribosomal frameshifting in yeast and mammalian in vitro translation systems, suggesting that they may have applications to control the propagation of viruses of higher eukaryotes, which also use this translational regulatory mechanism. Our results offer a new set of antiviral agents that may potentially have a broad range of applications in the clinical, veterinary, and agricultural fields.
Dinman
J D
JD
Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA. dinman@rwja.umdnj.edu
Ruiz-Echevarria
M J
MJ
Czaplinski
K
K
Peltz
S W
SW
D000841:Anisomycin / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D018965:Frameshifting, Ribosomal / Q000187:drug effects*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012328:RNA Viruses / Q000187:drug effects / Q000235:genetics*; D012441:Saccharomyces cerevisiae; D013033:Sparsomycin / Q000494:pharmacology*
D000998:Antiviral Agents; D011500:Protein Synthesis Inhibitors; D000841:Anisomycin; D013033:Sparsomycin; D010458:Peptidyl Transferases