Antiviral activity and mode of action of ribavirin 5'-sulfamate against Semliki Forest virus.
Ribavirin 5'-sulfamate, a nucleotide analog, inhibited Semliki Forest virus cytopathology by 50% at 10 microM, whereas ribavirin was inactive at less than or equal to 1 mM. Actinomycin D did not reverse (antagonize) the effect of ribavirin 5'-sulfamate against the virus. The compound inhibited amino acid incorporation into macromolecules of uninfected cells but had no appreciable effect on uridine incorporation. Infected cells treated with actinomycin D and nucleotide analog were inhibited in amino acid and uridine incorporation. The compound blocked the formation of the viral RNA polymerase protein in cells, which could account for the inhibited synthesis of new viral RNA. By electrophoresis, inhibition of the synthesis of viral proteins was more pronounced than the inhibition of cellular polypeptides. The analog inhibited the translation of mRNA to protein. Most animals treated intraperitoneally for 7 days with ribavirin 5'-sulfamate at 20 and 40 mg/kg/day starting 2 h before intraperitoneal Semliki Forest virus inoculation survived the otherwise lethal infection.
Smee
D F
DF
Nucleic Acid Research Institute, Costa Mesa, California 92626.
Alaghamandan
H A
HA
Kini
G D
GD
Robins
R K
RK
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D003609:Dactinomycin / Q000494:pharmacology; D005260:Female; D051379:Mice; D015394:Molecular Structure; D014176:Protein Biosynthesis / Q000187:drug effects; D011691:Puromycin / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D012367:RNA, Viral / Q000096:biosynthesis / Q000187:drug effects; D012254:Ribavirin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D012263:Ribonucleosides / Q000494:pharmacology*; D012672:Semliki forest virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D014036:Togaviridae Infections / Q000188:drug therapy*; D014709:Vero Cells
D000998:Antiviral Agents; D012333:RNA, Messenger; D012367:RNA, Viral; D012263:Ribonucleosides; C059925:ribavirin 5'-sulfamate; D003609:Dactinomycin; D012254:Ribavirin; D011691:Puromycin; D012321:DNA-Directed RNA Polymerases