The antiviral activity of the synthetic nucleoside, Virazole (1-io-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-' 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 106 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 10-6 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.The synthesis and development of a broad spectrum antiviral agent has been a challenging task because of the intimate association of virus replication and biochemical processes of the host cell. In addition, such an agent must inhibit a step in the process of virus replication that is common to a wide variety of RNA and DNA viruses (1). The synthesis and broad spectrum antiviral activity of 1-i3-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (I, Virazole) have recently been reported (1,2).

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We report on a new synthesis of several novel 6substituted derivatives of 9-,8-D-ribofuranosylpurine 3',5'cyclic phosphate. These analogs were shown to be more readily cleaved by rabbit kidney and pig brain phosphodiesterase than the corresponding 8-substituted compounds (viz., 8-SH, SCH3, SC2Hs, SCH2C6H5) previously reported upon. In addition, several of the 6-alkylthio derivatives were up to two times more active than cAMP as alternate activators

The extreme halophilic bacterium Halobacterium cutirubrum was examined for base, nucleoside, and nucleotide aminohydrolase activity on pyrimidine bases and their nucleosides and nucleotides. Only adenosine aminohydrolase activity was demonstrated. The enzyme was extracted from the cells and purified about 70-fold by liquid polymer two-phase fractionation, ammonium sulfate precipitation, and gel filtration. The enzyme has an apparent Km for adenosine of 4 × 10−5 M. The optimum pH is 7.5. The enzyme requires 4.0 M NaCl for maximal activity, but is irreversibly inactivated regardless of the concentration of NaCl when stored for extended periods of time.

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