Inhibitors of infectious pancreatic necrosis virus (IPNV) replication.

Abstract

In attempts to detect inhibitors of infectious pancreatic necrosis virus (IPNV) replication, we have evaluated, by an IPNV plaque inhibition assay, a group of compounds that have broad spectrum antiviral activity for both single- and double-stranded RNA viruses. The inosine monophosphate dehydrogenase (IMP dehydrogenase) inhibitors 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) and 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), and the orotidine monophosphate decarboxylase (OMP decarboxylase) inhibitor 4-hydroxy-3-beta-D-ribofuranosylpyrazole-5-carboxamide (pyrazofurin), were found to inhibit IPNV replication. For EICAR and pyrazofurin the concentrations that inhibited the IPNV plaque formation by 50% (EC50) were 0.01 micrograms/ml and 0.5 micrograms/ml, respectively. The cytotoxic concentrations required to reduce cell viability by 50% (CC50) were 50 micrograms/ml and 100 micrograms/ml, respectively, and the concentrations that reduced [methyl-3H] thymidine incorporation by 50% (IC50) were 0.5-1 and 50 micrograms/ml. Thus, for both compounds the IPNV-inhibitory concentration was 50-100 times lower than the concentration that affected DNA synthesis in growing cells. EICAR and pyrazofurin seem to be good candidates for further evaluation in an in vivo model of IPNV infection.

• Authors: M Jashés, M González, M López-Lastra, E De Clercq, A Sandino
• Journal: Antiviral research (Antiviral Res) Vol. 29 Issue 2-3 Pg. 309-12 (Mar 1996) ISSN: 0166-3542 [Print] Netherlands
• PMID: 8739609 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Antiviral Agents
• Pyrazoles
• Ribonucleosides
• 5-ethynyl-1-ribofuranosylimidazole-4-carboxamide
• 5'-noraristeromycin
• aristeromycin
• Foscarnet
• Ribavirin
• pyrazofurin
• 3-deazaneplanocin
• Ribose
• DNA
• IMP Dehydrogenase
• Hydrolases
• Adenosylhomocysteinase
• Orotidine-5'-Phosphate Decarboxylase
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Adenosylhomocysteinase
• Amides
• Animals
• Antiviral Agents (pharmacology)
• Cell Line
• DNA (drug effects)
• Foscarnet (pharmacology)
• Hydrolases (antagonists & inhibitors)
• IMP Dehydrogenase (antagonists & inhibitors)
• Infectious pancreatic necrosis virus (drug effects, growth & development, physiology)
• Orotidine-5'-Phosphate Decarboxylase (antagonists & inhibitors)
• Pyrazoles
• Ribavirin (pharmacology)
• Ribonucleosides (pharmacology)
• Ribose
• Salmon
• Viral Plaque Assay
• Virus Replication (drug effects)