Inhibitors of infectious pancreatic necrosis virus (IPNV) replication

Jashes, M.; Gonzalez, M.; Lopez-Lastra, M; Sandino,A; De Clercq, E

Keywords: dehydrogenase, inhibition, dna, animals, synthesis, assay, cell, cytotoxicity, beta, viability, embryo, virus, line, agents, inhibitor, salmonidae, ribavirin, agent, salmon, necrosis, replication, rna, pancreas, foscarnet, drug, adenosine, article, viruses, plaque, thymidine, decarboxylase, activity, concentration, controlled, radioisotope, imp, animal, hydrolases, pancreatic, infectious, study, 3, antiviral, response, carbenoxolone, priority, nonhuman, journal, Animalia, 5', a, unclassified, Monophosphate, deazaneplanocin, noraristeromycin, 6', fluoroaristeromycin, antivirus, brefeldin, inosinate, orotidine, pyrazofuran, birnaviridae, Adenosylhomocysteinase, Orotidine-5'-Phosphate, Ribonucleosides


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-?-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) and 5-ethynyl-1-?-D-ribofuranosylimidazole-4-carboxamide (EICAR), and orotidine monophosphate decarboxylase (OMP decarboxylase) inhibitor 4-hydroxy-3-?-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% (EC 50) were 0.01 ?g/ml and 0.5 ?g/ml, respectively. The cytotoxic concentrations required to reduce cell viability by 50% (CC 50) were 50 ?g/ml and 100 ?g/ml, respectively, and the concentrations that reduced [methyl- 3H] thymidine incorporation by 50% (IC 50) were 0.5-1 and 50 ?g/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.

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Título de la Revista: ANTIVIRAL RESEARCH
Volumen: 29
Número: 2-3
Fecha de publicación: 1996
Página de inicio: 309
Página final: 312