Jashés M, González M, López-Lastra M, De Clercq E, Sandino A
Departamento de Ciencias Biológicas, Facultad de Química y Biología, Universidad de Santiago de Chile, Chile.
Antiviral Res. 1996 Mar;29(2-3):309-12. doi: 10.1016/0166-3542(96)80226-9.
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.
为了检测传染性胰腺坏死病毒（IPNV）复制的抑制剂，我们通过IPNV蚀斑抑制试验评估了一组对单链和双链RNA病毒均具有广谱抗病毒活性的化合物。发现肌苷单磷酸脱氢酶（IMP脱氢酶）抑制剂1-β-D-呋喃核糖基-1,2,4-三唑-3-甲酰胺（利巴韦林）和5-乙炔基-1-β-D-呋喃核糖基咪唑-4-甲酰胺（EICAR），以及乳清苷单磷酸脱羧酶（OMP脱羧酶）抑制剂4-羟基-3-β-D-呋喃核糖基吡唑-5-甲酰胺（吡唑呋林）可抑制IPNV复制。对于EICAR和吡唑呋林，抑制IPNV蚀斑形成50%（EC50）的浓度分别为0.01微克/毫升和0.5微克/毫升。使细胞活力降低50%（CC50）所需的细胞毒性浓度分别为50微克/毫升和100微克/毫升，使[甲基-3H]胸苷掺入减少50%（IC50）的浓度分别为0.5 - 1微克/毫升和50微克/毫升。因此，对于这两种化合物，IPNV抑制浓度比影响生长细胞中DNA合成的浓度低50 - 100倍。EICAR和吡唑呋林似乎是在IPNV感染的体内模型中进行进一步评估的良好候选物。
