Antiviral Activity and Mode of Action Studies of Ribavirin and Mycophenolic Acid against Orthopoxviruses <i>in Vitro</i>

Smee, Donald F.; Bray, Mike; Huggins, John W.

doi:10.1177/095632020101200602

Cited by 83 publications

(68 citation statements)

References 37 publications

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“…In cultured cells, it is known to block the replication of positive-and negative-stranded RNA viruses and some DNA viruses (26,37). It has previously been reported to inhibit HDV replication in cultured primary woodchuck hepatocytes (8).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have proposed that the effects of ribavirin on virus replication are mediated primarily by depletion of the GTP pool; it is known that ribavirin inhibits an essential step leading to GTP formation (26,37). Specifically, ribavirin monophosphate is considered to be a competitive inhibitor of IMP dehydrogenase (IMPDH), the enzyme that converts IMP to xanthine monophosphate.…”

Section: Vol 80 2006 Accumulation Of Processed Hdv Rnas 3207mentioning

confidence: 99%

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Action of Inhibitors on Accumulation of Processed Hepatitis Delta Virus RNAs

Chang

Nie

Gudima

et al. 2006

J Virol

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Hepatitis delta virus (HDV) replication involves processing and accumulation of three RNA species: the genome, its exact complement (the antigenome), and a polyadenylated mRNA that acts as a template for the small delta antigen (␦Ag), the only protein of HDV and essential for genome replication. In a recently reported experimental system, addition of tetracycline induced synthesis of a DNA-directed source of ␦Ag, producing within 24 h a significant increase in accumulation of newly transcribed and processed HDV RNAs. This induction was used here to study the action of various inhibitors on accumulation. For example, potent and HDV-specific inhibition, in the absence of detected host toxicity, could be obtained with ribavirin, mycophenolic acid, and viramidine. An interpretation is that these inhibitors reduced the available GTP pool, leading to a specific inhibition of the synthesis and accumulation of HDV RNA-directed RNA species. In contrast, no inhibition was observed with L-FMAU (2-fluoro-5-methyl-␤-L-arabinofuranosyl-uridine), alpha interferon, or pegylated alpha interferon. After modifications to the experimental system, it was also possible to examine the effects of three known host RNA polymerase inhibitors on HDV genome replication: amanitin, 5,6-dichloro-1-␤-D-ribofuranosylbenzimidazole (DRB), and actinomycin. Of most interest, amanitin at low doses blocked accumulation of HDV RNA-directed mRNA but had less effect on HDV genomic and antigenomic RNAs. Additional experiments indicated that this apparent resistance to amanitin inhibition of genomic and antigenomic RNA relative to mRNA may not reflect a difference in the transcribing polymerase but rather relative differences in the processing and stabilization of nascent RNA transcripts.The 1,679-nucleotide, single-stranded, circular RNA genome of hepatitis delta virus (HDV) is replicated by RNAdirected RNA transcription mediated by a host polymerase (7). During replication, nascent RNA transcripts are processed to produce three different RNAs. The RNA genome and its exact complement, the antigenome, both arise from greaterthan-unit-length RNA linear transcripts that are reduced to unit length by ribozyme processing and then converted to a circular conformation by RNA ligation. An alternative processing of antigenomic RNA transcripts involves 5Ј capping and 3Ј polyadenylation to produce an mRNA of about 800 nucleotides in length. It is translated to produce a 195-aminoacid species, the small delta antigen (␦Ag), which is known to be essential for HDV replication (6). The features of HDV RNA transcription and processing have been incorporated into what is referred to as a double rolling-circle model (39).In order to study HDV replication experimentally, it is possible to infect primary hepatocyte cultures (2, 38). Such culture systems are somewhat inconvenient, but, as yet, infection of established cell lines has not been reported. The replication of the HDV genome can however be studied with cell lines following transfection with HDV RNAs or cDNA (39). Re...

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Section: Discussionmentioning

confidence: 99%

Section: Vol 80 2006 Accumulation Of Processed Hdv Rnas 3207mentioning

confidence: 99%

Action of Inhibitors on Accumulation of Processed Hepatitis Delta Virus RNAs

Chang

Nie

Gudima

et al. 2006

J Virol

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“…Determinations of the antiviral activities of the four 5-halo-2′-deoxyuridine compounds were made in 12-well microplates of confluent C127I, LLC-MK 2 and A549 cells by plaque reduction assay, as previously described, using multiple half-log 10 dilutions of test compound [9]. Cytotoxicity assays were performed using semi-confluent cell monolayers in 24-well microplates.…”

Section: Plaque Reduction Cytotoxicity and Virus Yield Reduction Assaysmentioning

confidence: 99%

Antiviral Activities and Phosphorylation of 5-halo-2'-Deoxyuridines and N-Methanocarbathymidine in Cells Infected with Vaccinia Virus

Smee

Humphreys

Hurst

et al. 2008

Antivir Chem Chemother

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It has long been recognized that herpes simplex virus thymidine kinase (TK) is able to phosphorylate certain nucleoside analogues to their monophosphate forms in infected cells, whereas host cells do this poorly [1,2]. This effect has led to the identification of selective antiviral compounds, some of which have been developed as drugs, including idoxuridine, acyclovir, ganciclovir and penciclovir [3]. The herpes simplex virus possesses a type I TK that has a broader substrate specificity than the host cell type II TK and orthopoxvirus type II TK [4,5]. Because of the narrow substrate specificity of poxvirus TK, there have been few discoveries of compounds that are selectively phosphorylated by poxvirus TK. Prichard and colleagues [6,7] presented evidence that the antiviral potencies of 5-bromo-2′-deoxyuridine (BrdU), 5-iodo-2′-deoxyuridine (IdU) and N-methanocarbathymidine [(N)-MCT] were greater against TK-containing (TK + ) cowpox virus than against TK-deficient (TK -) cowpox virus. This suggested that the compounds were activated by cowpox virus TK and gave an indication that the poxvirus TK differs slightly from host cell TK in substrate specificity. This feature of the virus may be exploited to identify selective new poxvirus inhibitors. Indeed, Prichard and colleagues [8] later reported a series of 2′-deoxyuridine derivatives whose antiviral activity was highly dependent upon poxvirus TK.The antipoxvirus activities of certain compounds may be dependent upon the cell line in which the assay was conducted. For example, we found that BrdU was more potent against TK + than TK -vaccinia virus, but this effect was only seen in Vero monkey cells and A549

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“…But not significant inhibiton of level, ribavirin was more to toxic to replicating cells than to stationary cell monolayers in Vero cells. 18 Currently, there is no published data on the possible anti-DENV activities of Copper and copper compounds. In the present study, we investigated of Copper(II)chloride Dihydrate antiviral compound were futher tested for inhibitory effect on the replication of DENV-2 in cell culture.…”

Section: Infeksi Virus Dengue (Denv) Adalah Patogen Yang Muncul Secarmentioning

confidence: 99%

Antiviral Activity of Copper(ii)chloride Dihydrate Against Dengue Virus Type-2 in Vero Cell

Sucipto

Churrotin

Setyawati

et al. 2017

IJTID

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Infection of dengue virus (DENV) was number of globally significant emerging pathogen. Antiviral dengue therapies are importantly needed to control emerging dengue. Dengue virus (DENV) is mosquito-borne arboviruses responsible for causing acute systemic diseases and grievous health conditions in humans. To date, there is no clinically approved dengue vaccine or antiviral for humans, even though there have been great efforts towards this end. Copper and copper compounds have more effective in inactivation viruses, likes an influenza virus and human immunodeficiency virus (HIV). Purpose in this project was investigated of Infeksi virus dengue (DENV) adalah patogen yang muncul secara global. Terapi antivirus dengue penting diperlukan untuk mengontrol muncul dengue. Dengue virus (DENV) disebabkan oleh mosquito-borne arboviruses yang menyebabkan penyakit sistemik akut dan kondisi kesehatan pada manusia. Sampai saat ini, tidak ada vaksin dengue klinis disetujui atau antivirus bagi manusia, meskipun telah ada upaya besar menjelang akhir ini. Tembaga dan senyawa tembaga memiliki efektivitas dalam inaktivasi virus, seperti virus influenza dan human immunodeficiency virus (HIV). Tujuan dalam proyek ini adalah menyelidiki senyawa antiviral

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Antiviral Activity and Mode of Action Studies of Ribavirin and Mycophenolic Acid against Orthopoxviruses in Vitro

Cited by 83 publications

References 37 publications

Action of Inhibitors on Accumulation of Processed Hepatitis Delta Virus RNAs

Action of Inhibitors on Accumulation of Processed Hepatitis Delta Virus RNAs

Antiviral Activities and Phosphorylation of 5-halo-2'-Deoxyuridines and N-Methanocarbathymidine in Cells Infected with Vaccinia Virus

Antiviral Activity of Copper(ii)chloride Dihydrate Against Dengue Virus Type-2 in Vero Cell

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