Synergistic Antiviral Activity of Inhibitors of S-Adenosylhomocysteine Hydrolase and Ribavirin
| Autor: | M. Hasobe, James G. McKee, Ronald T. Borchardt, H. Ishii, D. B. Ault-Riche |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification GTP' Ribavirin 030106 microbiology General Medicine Biology 01 natural sciences 0104 chemical sciences 010404 medicinal & biomolecular chemistry 03 medical and health sciences chemistry.chemical_compound Enzyme chemistry Biochemistry IMP dehydrogenase Enzyme inhibitor Hydrolase biology.protein Adenosylhomocysteinase Nucleoside |
| Zdroj: | Antiviral Chemistry and Chemotherapy. 4:127-130 |
| ISSN: | 2040-2066 |
| DOI: | 10.1177/095632029300400207 |
| Popis: | (1′R,2′S,3′R)-9-(2′,3′-Dihydroxycycloperrt-4′-en-1′-yl)-adenine (DHCeA) and -3-deazaadenine (3-deaza-DHCeA), which are potent inhibitors of S-adenosylho-mocysteine (AdoHcy) hydrolase, and ribavirin, which is an inhibitor of IMP-dehydrogenase, were found in this study to have synergistic effects on inhibiting vaccinia virus replication in murine L929 cells without creating a synergistic effect on cellular toxicity. Thus, the antiviral effectiveness of this drug combination was 5–10× higher than the antiviral effectiveness observed with the AdoHcy hydrolase inhibitors alone. Ribavirin does not alter the ability of DHCeA and 3-deaza-DHCeA to elevate the intracellular AdoHcy/S-adeno-sylmethionine (AdoMet) ratio. Increases in this ratio were shown earlier to correlate with the antiviral effects of these carbocyclic nucleosides. Ribavirin was also shown to significantly reduce the cellular level of GTP, which is consistent with its activity as an inhibitor of IMP-dehydrogenase and its proposed mechanism of antiviral action, inhibiting the formation of the ‘capped methylated structure’ at the 5′-end of viral mRNA. |
| Databáze: | OpenAIRE |
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