Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

3-Nitro-3-deazauridine (3N-3DU) is a new synthetic nucleoside having activity against members of 5 RNA virus families including: paramyxoviruses (parainfluenza, PIV), picornaviruses (rhino-, RV), rhabdoviruses (vesicular stomatitis, VSV), togaviruses (Semliki Forest, SFV) and bunyaviruses (Punta Toro, PTV). In this report, we evaluate and compare its activity with the parent nucleoside, 3-deazauridine (3DU) and ribavirin as drug standards. Comparison of drug activities utilizes observations of antiviral indices, which are determined by the following formula: maximum tolerated dose (MTD)/minimum inhibitory concentration (MIC). The antiviral index (AI) of 3N-3DU (AI 15.3) was comparable to ribavirin and much higher than 3DU when evaluated against PIV. The 3N-3DU was the most active of the three when tested against RV (AI 24.1), SFV (AI 76.9) or VSV (AI 50). In contrast to the RV activity, 3N-3DU (AI 0.5) and 3DU (AI less than 0.1) were less active than ribavirin (AI 1.3) when evaluated against poliovirus, type 1 (PoV). Ribavirin (AI 10.0) was more active than 3N-3DU (AI 2.4) and 3DU (AI less than 0.1) against PTV. 3N-3DU exhibited comparable toxicity to ribavirin in KB cells, was 4-fold less toxic in WISH cells and 4-fold more toxic in LLC-MK2 cells. Overall, 3N-3DU is markedly less toxic than its parent nucleoside, 3DU. It appears from this study that the structural modification of 3DU resulting from the addition of the nitro group in the 3 position of the base reduces toxicity and enhances the antiviral activity.
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PMID:Antiviral and cytotoxicity evaluation of 3-nitro-3-deazauridine. 263 63

The effect of phosphorylated ribavirin on a vesicular stomatitis virus (VSV) in vitro transcription reaction was examined. Viral mRNA synthesized in the presence of the 5' mono-, di-, and triphosphorylated forms of the drug translated with equal efficiencies under the test conditions. However, all three phosphorylated species inhibited VSV transcription. The mono- and diphosphorylated forms of the drug possessed approximately two to three times the inhibitory activity as the triphosphorylated form. Transcripts synthesized in the presence of drug were full length and were absent of incorporated drug. Inhibition by ribavirin 5'-diphosphate could be reversed by the addition of UTP, CTP, and GTP, while the addition of GDP to the reaction did not reverse inhibition. Ribavirin diphosphate was added to a La Crosse virus in vitro transcription assay to determine whether an inhibitory effect could be established in a viral system that was more sensitive to ribavirin than was VSV; it led to profound inhibition of RNA synthesis at concentrations as low as 0.1 microgram/ml. These data suggest that ribavirin has an effect on the initial steps of transcription by some RNA-dependent RNA polymerases and that this effect may be mediated by several phosphorylated forms.
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PMID:Effect of phosphorylated ribavirin on vesicular stomatitis virus transcription. 283 39

Ribavirin at 200 micrograms/ml inhibited vesicular stomatitis virus (VSV) growth in Chinese hamster ovary (CHO) cells by 2.5 logs. To determine the mechanism of this inhibition, viral macromolecular synthesis was examined. VSV primary transcription remained unaffected, but overall VSV RNA synthesis decreased by 40 to 60%. When ribavirin was added 1.5 h after infection, inhibition of progeny production was partially lost, indicating that the antiviral effect was on an early stage after primary transcription. Inhibition of RNA polymerization by premature chain termination was not evident. Viral translation, on the other hand, was reduced by 95% with an inhibition of every protein species. Furthermore, viral RNA synthesized in the presence of ribavirin did not translate well in an in vitro translation system. In contrast, uninfected CHO cells treated with ribavirin showed a greater sensitivity in RNA synthesis than in protein synthesis. This suggests that the cellular translational machinery was not directly affected. Short-term treatment of cells resulted in negligible toxicity, but after 24 h there was marked alteration of cellular integrity. These results, taken together with data on other viruses, suggest that in the presence of ribavirin, dysfunctional VSV mRNA was synthesized, resulting in its failure to be translated. The selective antiviral effects of ribavirin and its relative lack of toxicity for host cells may be predicted on the basis of mRNA turnover and the requirements for de novo functional mRNA.
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PMID:Effect of ribavirin on macromolecular synthesis in vesicular stomatitis virus-infected cells. 301 12

Virazole (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a highly soluble new synthetic nucleoside having significant, reproducible activity against a broad spectrum of deoxyribonucleic acid and ribonucleic acid viruses in vitro. The drug inhibited viral cytopathogenic effects in monolayers of cells infected for 3 days with type 3 adeno, types 1 and 2 herpes, myxoma, cytomegalo, vaccinia, infectious bovine rhinotracheitis, types 1A, 2, 8, 13, and 56 rhino, types 1 and 3 parainfluenza, vesicular stomatitis, subacute sclerosing panencephalitis, Semliki Forest, Newcastle disease, and measles viruses. Hemagglutinin production by influenza A(2), influenza B, and type 1 parainfluenza viruses in chicken embryo cells was reduced by Virazole treatment. Recoverable intra- and extracellular virus titers were reduced by the drug in experiments with type 1 herpes, vaccinia, type 3 parainfluenza, and vesicular stomatitis viruses. Plaque formation by type 1 herpesvirus was also inhibited by exposure of the infected cells to Virazole. Pretreatment of cells with the compound, followed by its removal before addition of type 1 herpesvirus, severely lessened the antiviral activity; the compound was still moderately effective in reducing the viral effects on the cells when added as long as 22 hr after the virus. Parallel experiments, in which the antiviral activity of a number of known active drugs was compared, indicated Virazole to have at least a comparable degree of activity, and it was also active against a wider variety of viruses than any of these known active materials. The CCED(50) of Virazole to chicken embryo cells was approximately 1,000 mug/ml, although concentrations as low as 10 mug/ml caused slight (15%) inhibition in total cellular protein after 72 hr of incubation.
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PMID:In vitro effect of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole, ICN 1229) on deoxyribonucleic acid and ribonucleic acid viruses. 420 81

Virazole is a synthetic nucleoside active in tissue culture against at least 16 DNA and RNA viruses. Applied topically, it inhibits herpetic keratitis in rabbits and tail lesions induced by herpes, vaccinia, and vesicular stomatitis viruses in mice. Injected intraperitoneally into mice, it inhibits splenomegaly and hepatomegaly induced by Friend leukemia virus and respiratory infections caused by influenza A(O), A(2), and B viruses and parainfluenza 1 virus. infections is also effective.
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PMID:Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide. 434 Sep 49

The effect of virazole on the antiviral activity of poly (G) X poly (C), poly (G, A) X X poly (C) and poly(G, I) X poly (C) was studied in cell cultures and on mice. It was shown that virazole in concentrations not sufficient for significant inhibition of the development of vesicular stomatitis virus or Sindbis virus in chick embryo cell cultures markedly increased the antiviral effect and allowed decreasing the minimum effective doses of the synthetic polyribonucleotide complexes with respect to the above viruses. Combined administration of poly (G) X poly (C) and virazole to mice 1-2 or 24 hours after infection with tick-borne encephalitis virus provided a much more pronounced decrease in the death rate of the animals than the use of the interferonogen alone. Virazole per se was little active and had no significant effect on the intensity of interferonogenesis promoted by the use of poly (G) X poly (C). A possibility of successful therapy of viral infections with polyribonucleotide interferonogens in combination with virazole or other chemotherapeutic drugs with broad antiviral spectrum is discussed.
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PMID:[Effect of virazole on the antiviral activity of poly(G) X poly(C) and other polyribonucleotide interferonogens]. 608 50

Ribavirin (RBV) is a synthetic nucleoside analog with broad spectrum antiviral activity. Although RBV is approved for the treatment of hepatitis C virus, respiratory syncytial virus, and Lassa fever virus infections, its mechanism of action and therapeutic efficacy remains highly controversial. Recent reports show that the development of cell-based resistance after continuous RBV treatment via decreased RBV uptake can greatly limit its efficacy. Here, we examined whether certain cell types are naturally resistant to RBV even without prior drug exposure. Seven different cell lines from various host species were compared for RBV antiviral activity against two nonsegmented negative-strand RNA viruses, vesicular stomatitis virus (VSV, a rhabdovirus) and Sendai virus (SeV, a paramyxovirus). Our results show striking differences between cell types in their response to RBV, ranging from virtually no antiviral effect to very effective inhibition of viral replication. Despite differences in viral replication kinetics for VSV and SeV in the seven cell lines, the observed pattern of RBV resistance was very similar for both viruses, suggesting that cellular rather than viral determinants play a major role in this resistance. While none of the tested cell lines was defective in RBV uptake, dramatic variations were observed in the long-term accumulation of RBV in different cell types, and it correlated with the antiviral efficacy of RBV. While addition of guanosine neutralized RBV only in cells already highly resistant to RBV, actinomycin D almost completely reversed the RBV effect (but not uptake) in all cell lines. Together, our data suggest that RBV may inhibit the same virus via different mechanisms in different cell types depending on the intracellular RBV metabolism. Our results strongly point out the importance of using multiple cell lines of different origin when antiviral efficacy and potency are examined for new as well as established drugs in vitro.
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PMID:Cell type mediated resistance of vesicular stomatitis virus and Sendai virus to ribavirin. 2058 19