In Vitro Antiviral Activity of 6-Substituted 9-β-
            <scp>d</scp>
            -Ribofuranosylpurine 3′,5′-Cyclic Phosphates

Sidwell, Robert W.; Huffman, John H.; Allen, Lois B.; Meyer, Rich B.; Shuman, Dennis A.; Simon, Lionel N.; Robins, Roland K.

doi:10.1128/aac.5.6.652

Cited by 10 publications

(2 citation statements)

References 16 publications

(16 reference statements)

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“…Rib has been documented to be a broad-spectrum antiviral drug active against a variety of RNA viruses (Sidwell et al 1974;Streeter et al 1973). Several mechanisms of action have been proposed for the antiviral activity of Rib including direct incorporation into the RNA during replication, alteration of dNTP pools through IMPDH inhibition, direct inhibition of RNA synthesis, RNA capping inhibition, and immunomodulation (Graci and Cameron 2006).…”

Section: Advantages Of Combination Versus Single Drugmentioning

confidence: 99%

Arenavirus Quasispecies and Their Biological Implications

Grande-Pérez

Martı́n

Moreno

et al. 2015

Current Topics in Microbiology and Immunology

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The family Arenaviridae currently comprises over 20 viral species, each of them associated with a main rodent species as the natural reservoir and in one case possibly phyllostomid bats. Moreover, recent findings have documented a divergent group of arenaviruses in captive alethinophidian snakes. Human infections occur through mucosal exposure to aerosols or by direct contact of abraded skin with infectious materials. Arenaviruses merit interest both as highly tractable experimental model systems to study acute and persistent infections and as clinically important human pathogens including Lassa (LASV) and Junin (JUNV) viruses, the causative agents of Lassa and Argentine hemorrhagic fevers (AHFs), respectively, for which there are no FDA-licensed vaccines, and current therapy is limited to an off-label use of ribavirin (Rib) that has significant limitations. Arenaviruses are enveloped viruses with a bi-segmented negative strand (NS) RNA genome. Each genome segment, L (ca 7.3 kb) and S (ca 3.5 kb), uses an ambisense coding strategy to direct the synthesis of two polypeptides in opposite orientation, separated by a noncoding intergenic region (IGR). The S genomic RNA encodes the virus nucleoprotein (NP) and the precursor (GPC) of the virus surface glycoprotein that mediates virus receptor recognition and cell entry via endocytosis. The L genome RNA encodes the viral RNA-dependent RNA polymerase (RdRp, or L polymerase) and the small (ca 11 kDa) RING finger protein Z that has functions of a bona fide matrix protein including directing virus budding. Arenaviruses were thought to be relatively stable genetically with intra- and interspecies amino acid sequence identities of 90-95 % and 44-63 %, respectively. However, recent evidence has documented extensive arenavirus genetic variability in the field. Moreover, dramatic phenotypic differences have been documented among closely related LCMV isolates. These data provide strong evidence of viral quasispecies involvement in arenavirus adaptability and pathogenesis. Here, we will review several aspects of the molecular biology of arenaviruses, phylogeny and evolution, and quasispecies dynamics of arenavirus populations for a better understanding of arenavirus pathogenesis, as well as for the development of novel antiviral strategies to combat arenavirus infections.

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Section: Advantages Of Combination Versus Single Drugmentioning

confidence: 99%

Arenavirus Quasispecies and Their Biological Implications

Grande-Pérez

Martı́n

Moreno

et al. 2015

Current Topics in Microbiology and Immunology

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“…[8][9][10][11] Several HIV-1 TOA assays have been described in the literature. 10,[12][13][14][15][16][17] In these assays, cells are infected with HIV-1 at a high multiplicity of infection (MOI) for 1-2 h, after which the unbound virus is removed by washing.…”

Section: Introductionmentioning

confidence: 99%

An Automated Time-of-Drug-Addition Assay to Routinely Determine the Mode of Action of HIV-1 Inhibitors

Loock

Eynde

Hansen

et al. 2013

ASSAY and Drug Development Technologies

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Cell-based high-throughput screening campaigns are widely used to identify novel antiviral compounds, for example, against human immunodeficiency virus type 1 (HIV-1). Typically, these assays enable identification of compounds that potentially target any viral or cellular factor involved in the viral replication cycle. Unraveling the mechanism of action of these active compounds is an important step to facilitate further drug development. Time-of-addition (TOA) assays are an elegant tool to achieve this goal by comparing the TOA profile of novel compounds with those of well-studied reference compounds. Downscaling to a 384-well format and automation significantly increase the capacity of the TOA assay, enabling compound handling around the clock. Mechanical liquid dispensing with optimized time points for compound addition ensures robustness (Z'>0.8) and maximal resolution in profiling novel antiviral compounds. The presented methodology has been optimized for routine use and allows for fully automated high-throughput screening to support the process in search for novel inhibitors of HIV-1.

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Rhinoviruses

Gwaltney

1989

Viral Infections of Humans

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In Vitro Antiviral Activity of 6-Substituted 9-β- d -Ribofuranosylpurine 3′,5′-Cyclic Phosphates

Cited by 10 publications

References 16 publications

Arenavirus Quasispecies and Their Biological Implications

Arenavirus Quasispecies and Their Biological Implications

An Automated Time-of-Drug-Addition Assay to Routinely Determine the Mode of Action of HIV-1 Inhibitors

Rhinoviruses

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