Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mycophenolic acid [the active metabolite of the immunosuppressive agent mycophenolate mofetil (MMF)] and ribavirin were found to potentiate the anti-HBV activity of the guanine-based nucleoside analogues penciclovir (PCV), lobucavir (LBV) and 3'-fluorodideoxyguanosine (FLG) and diaminopurine dioxolane (DAPD). Ribavirin and mycophenolic acid are both inhibitors of inosine 5'-monophosphate dehydrogenase and cause a depletion of intracellular dGTP levels. It may be assumed that the 5'-triphosphorylated derivatives of the guanine-based nucleoside analogues, in the presence of reduced levels of dGTP, inhibit more efficiently the priming reaction as well as the reverse transcription and DNA-dependent DNA polymerase activity of the HBV polymerase. This assumption is corroborated by the observation that exogenously added guanosine reversed the potentiating effect of ribavirin and mycophenolic acid on the anti-HBV activity of the guanosine analogues. Our observations may have implications for those (liver) transplant recipients that receive MMF as (part of their) immunosuppressive regimen and that, because of de novo or persistent infection with HBV, need specific anti-HBV therapy.
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PMID:Ribavirin and mycophenolic acid potentiate the activity of guanine- and diaminopurine-based nucleoside analogues against hepatitis B virus. 1111 13

Mycophenolic acid (MPA), the active form of the immunosuppressive agent mycophenolate mofetil (MMF), was found to markedly potentiate the anti-herpesvirus activity of the novel anti-herpesvirus agent A-5021, (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guanine. For example, at a concentration of 1 microg/ml MPA, the activity of A-5021 against HSV-1, HSV-2 and TK(-) HSV-1 increased by a factor of 130, 14 and > or = 189, respectively. Exogenously added guanosine reversed this potentiating effect, suggesting that a depletion of the endogenous dGTP pools enhanced the inhibitory effect of the 5'-triphosphate metabolite of A-5021 on the viral DNA polymerase. The combined effect of A-5021 and MPA on the growth of uninfected Vero cells was additive rather than synergistic. The combination of topically applied MMF (5%) with 0.05% A-5021 (a subactive concentration) completely protected against HSV-1-induced cutaneous lesions in hairless mice, whereas therapy with either compound used alone had no protective effect. These findings may have implications for those transplant recipients that receive MMF as (part of) their immunosuppressive therapy and that develop intercurrent herpesvirus infections for which they need treatment.
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PMID:The anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)-cycloprop-1'-yl]methyl]guanine is markedly potentiated by the immunosuppressive agent mycophenolate mofetil. 1124 64