期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1973
卷号：70
期号：4
页码：1174-1178
DOI：10.1073/pnas.70.4.1174
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The antiviral activity of the synthetic nucleoside, Virazole (1-{beta}-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), against measles virus in Vero cell cultures was substantially reversed by xanthosine, guanosine, and to a slightly lesser extent by inosine. Virazole 5'-phosphate was subsequently found to be a potent competitive inhibitor of inosine 5'-phosphate dehydrogenase (IMP:NAD+ oxidoreductase, EC 1.2.1.14 ) isolated from Escherichia coli (Km = 1.8 x 10-5 M) with a Ki of 2.7 x 10-7 M. Guanosine 5'-phosphate (GMP) was a competitive inhibitor of this enzyme with a Ki of 7.7 x 10-5 M. Virazole 5'-phosphate was similarly active against IMP dehydrogenase isolated from Ehrlich ascites tumor cells, with a Ki of 2.5 x 10-7 M. The Km for this enzyme was 1.8 x 10-5 M, and the Ki for GMP was 2.2 x 10-4 M. These results suggest that the antiviral activity of Virazole might be due to the inhibition of GMP biosynthesis in the infected cell at the step involving the conversion of IMP to xanthosine 5'-phosphate. This inhibition would consequently result in inhibition of the synthesis of vital viral nucleic acid.
