Inhibition of RNA Virus Replication in Vitro by 3-Deazacytidine and 3-Deazauridine

Khare, G. P.; Sidwell, Robert W.; Huffman, John H.; Tolman, Richard L.; Robins, Roland K.

doi:10.3181/00379727-140-36571

Cited by 26 publications

(10 citation statements)

References 2 publications

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“…(A preliminary report of this work was presented at the 56th Annual Meeting of the Federation of American Societies for Experimental Biology, Atlantic City, N.J., 9-14 April 1972.) MATERIALS (5).…”

mentioning

confidence: 99%

Suppression by 1-β- d -Ribofuranosyl-1,2,4-Triazole-3-Carboxamide (Virazole, ICN 1229) of Influenza Virus-Induced Infections in Mice

Khare¹,

Sidwell²,

Witkowski³

et al. 1973

Antimicrob Agents Chemother

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1-β- d -Ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole) was found to possess significant antiviral activity against aerosol-induced or intranasally induced influenza A 0 , A 2 , and B virus infections in mice. Significant protection was achieved by both oral and intraperitoneal routes of administration. Depending upon the level of virus infection, antiviral activity was best observed at the daily dose of 75 mg/kg. The efficacy of the compound was evidenced by an increase in survivor number, prolongation of mean survival time, suppression of lung consolidation, or decrease in hemagglutinin titer in the infected lung samples. The therapeutic value of this synthetic triazole nucleoside was evident as noted by a significant increase in survivor number even if the treatment was started as late as 24 h after infection with an aerosol of influenza A 2 virus.

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mentioning

confidence: 99%

Suppression by 1-β- d -Ribofuranosyl-1,2,4-Triazole-3-Carboxamide (Virazole, ICN 1229) of Influenza Virus-Induced Infections in Mice

Khare¹,

Sidwell²,

Witkowski³

et al. 1973

Antimicrob Agents Chemother

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“…Our study, to the best of our knowledge, is the first to demonstrate the antiretroviral activity of formycin A. Many previous studies identified the activity of 3-deazauridine against riboviruses (20)(21)(22)(23)(24)(25)(26) and retroviruses (23,27). Interestingly, 3-deazauridine was previously observed to potentiate the anti-HIV-1 activity of 3TC and dideoxycytosine (28).…”

Section: Discussionmentioning

confidence: 86%

Discovery of Novel Ribonucleoside Analogs with Activity against Human Immunodeficiency Virus Type 1

Dapp

Bonnac

Patterson

et al. 2014

J Virol

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Reverse transcription is an important early step in retrovirus replication and is a key point targeted by evolutionarily conserved host restriction factors (e.g., APOBEC3G, SamHD1). Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a major target of antiretroviral drugs, and concerns regarding drug resistance and off-target effects have led to continued efforts for identifying novel approaches to targeting HIV-1 RT. Several observations, including those obtained from monocytederived macrophages, have argued that ribonucleotides and their analogs can, intriguingly, impact reverse transcription. For example, we have previously demonstrated that 5-azacytidine has its greatest antiviral potency during reverse transcription by enhancement of G-to-C transversion mutations. In the study described here, we investigated a panel of ribonucleoside analogs for their ability to affect HIV-1 replication during the reverse transcription process. We discovered five ribonucleosides-8-azaadenosine, formycin A, 3-deazauridine, 5-fluorocytidine, and 2=-C-methylcytidine-that possess anti-HIV-1 activity, and one of these (i.e., 3-deazauridine) has a primary antiviral mechanism that involves increased HIV-1 mutational loads, while quantitative PCR analysis determined that the others resulted in premature chain termination. Taken together, our findings provide the first demonstration of a series of ribonucleoside analogs that can target HIV-1 reverse transcription with primary antiretroviral mechanisms that include premature termination of viral DNA synthesis or enhanced viral mutagenesis.

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“…The discovery of the activated intermediates of 14C-labeled 2-DG in BHK-21 cells indicates that the corresponding nucleoside diphosphate derivatives of UDP-2-DG and GDP-2-DG can be expected to contribute to the inhibition of the transglycosylation reactions during arboviral infections (4,7). The viral inhibitory activity of 3-deazaUR, shown to occur during viral replication, was reversed by the naturally occurring pyrimidine nucleoside (9). Metabolic studies have shown that 3-deazaUR, phosphorylated by leukemia L-1210 cells, exerts its inhibitory activity by interfering with the activity of the CTP synthetase (11).…”

Section: Resultsmentioning

confidence: 99%

“…Another compound that possesses significant antiviral activity against RNA viruses is the antipyrimidine, 3-deazauridine . Although 3-deazaUR greatly restricts host as well as viral RNA synthesis at high concentration, this compound has antiviral activity at noncytotoxic levels (9,11,16).…”

mentioning

confidence: 99%

Effects of 2-Deoxy- d -Glucose and 3-Deazauridine Individually and in Combination on the Replication of Japanese B Encephalitis Virus

Woodman

Williams

1977

Antimicrob Agents Chemother

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We have tested the potencies of the competitors of glucose, 2-deoxy-i>.glucose, and of uridine, 3-deazauridine, on the inhibition of Japanese B encephalitis virus multiplication in BHK-21 cell cultures. The relative effectiveness of the viral inhibitors were evaluated individually and in combination in relation to cytotoxicity as a measure of the selectivity of inhibition. When the drugs were administered individually, the antiviral activity was masked by the cytotoxic effect on the host. By combining the two drugs, it was possible to inhibit Japanese encephalitis virus production at noncytotoxic concentrations. The effects of 2-deoxy-D-glucose and 3-deazauridine on the growth inhibition of BHK-21 cells in cultures were only additive, while they were clearly synergistic on the inhibition of Japanese encephalitis virus production. Thus, it was possible 'to achieve an increased antiviral effect without a significant increase in cytotoxicity. Although the precise biochemical mechanism of the antiviral activity of these antimetabolites in combination is not known, our results indicate the potential value of this approach in viral chemotherapy.

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Inhibition of RNA Virus Replication in Vitro by 3-Deazacytidine and 3-Deazauridine

Cited by 26 publications

References 2 publications

Suppression by 1-β- d -Ribofuranosyl-1,2,4-Triazole-3-Carboxamide (Virazole, ICN 1229) of Influenza Virus-Induced Infections in Mice

Suppression by 1-β- d -Ribofuranosyl-1,2,4-Triazole-3-Carboxamide (Virazole, ICN 1229) of Influenza Virus-Induced Infections in Mice

Discovery of Novel Ribonucleoside Analogs with Activity against Human Immunodeficiency Virus Type 1

Effects of 2-Deoxy- d -Glucose and 3-Deazauridine Individually and in Combination on the Replication of Japanese B Encephalitis Virus

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