The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Joel Janin - One of the best experts on this subject based on the ideXlab platform.
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human and viral nucleoside nucleotide kinases involved in antiviral Drug Activation structural and catalytic properties
Antiviral Research, 2010Co-Authors: Dominique Devillebonne, Chahrazade El Amri, Philippe Meyer, Yuxing Chen, Luigi A Agrofoglio, Joel JaninAbstract:Abstract Antiviral nucleoside and nucleotide analogs, essential for the treatment of viral infections in the absence of efficient vaccines, are proDrug forms of the active compounds that target the viral DNA polymerase or reverse transcriptase. The Activation process requires several successive phosphorylation steps catalyzed by different kinases, which are present in the host cell or encoded by some of the viruses. These Activation reactions often are rate-limiting steps and are thus open to improvement. We review here the structural and enzymatic properties of the enzymes that carry out the Activation of analogs used in therapy against human immunodeficiency virus and against DNA viruses such as hepatitis B, herpes and poxviruses. Four major classes of Drugs are considered: thymidine analogs, non-natural l -nucleosides, acyclic nucleoside analogs and acyclic nucleoside phosphonate analogs. Their efficiency as Drugs depends both on the low specificity of the viral polymerase that allows their incorporation into DNA, but also on the ability of human/viral kinases to provide the activated triphosphate active forms at a high concentration at the right place. Two distinct modes of action are considered, depending on the origin of the kinase (human or viral). If the human kinases are house-keeping enzymes that belong to the metabolic salvage pathway, herpes and poxviruses encode for related enzymes. The structures, substrate specificities and catalytic properties of each of these kinases are discussed in relation to Drug Activation.
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Human and viral nucleoside/nucleotide kinases involved in antiviral Drug Activation: structural and catalytic properties.
Antiviral research, 2010Co-Authors: Dominique Deville-bonne, Chahrazade El Amri, Philippe Meyer, Yuxing Chen, Luigi A Agrofoglio, Joel JaninAbstract:Abstract Antiviral nucleoside and nucleotide analogs, essential for the treatment of viral infections in the absence of efficient vaccines, are proDrug forms of the active compounds that target the viral DNA polymerase or reverse transcriptase. The Activation process requires several successive phosphorylation steps catalyzed by different kinases, which are present in the host cell or encoded by some of the viruses. These Activation reactions often are rate-limiting steps and are thus open to improvement. We review here the structural and enzymatic properties of the enzymes that carry out the Activation of analogs used in therapy against human immunodeficiency virus and against DNA viruses such as hepatitis B, herpes and poxviruses. Four major classes of Drugs are considered: thymidine analogs, non-natural l -nucleosides, acyclic nucleoside analogs and acyclic nucleoside phosphonate analogs. Their efficiency as Drugs depends both on the low specificity of the viral polymerase that allows their incorporation into DNA, but also on the ability of human/viral kinases to provide the activated triphosphate active forms at a high concentration at the right place. Two distinct modes of action are considered, depending on the origin of the kinase (human or viral). If the human kinases are house-keeping enzymes that belong to the metabolic salvage pathway, herpes and poxviruses encode for related enzymes. The structures, substrate specificities and catalytic properties of each of these kinases are discussed in relation to Drug Activation.
Avidan U. Neumann - One of the best experts on this subject based on the ideXlab platform.
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Correction: Novel decay dynamics revealed for virus-mediated Drug Activation in cytomegalovirus infection.
PLoS pathogens, 2017Co-Authors: Jessica Rose, Vincent C. Emery, Deepali Kumar, Anders Åsberg, Anders Hartmann, Alan G. Jardine, Angelo A. Bignamini, Atul Humar, Avidan U. NeumannAbstract:[This corrects the article DOI: 10.1371/journal.ppat.1006299.].
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Novel decay dynamics revealed for virus-mediated Drug Activation in cytomegalovirus infection.
PLoS pathogens, 2017Co-Authors: Jessica Rose, Vincent C. Emery, Deepali Kumar, Anders Åsberg, Anders Hartmann, Alan G. Jardine, Angelo A. Bignamini, Atul Humar, Avidan U. NeumannAbstract:Human cytomegalovirus (CMV) infection is a substantial cause of morbidity and mortality in immunocompromised hosts and globally is one of the most important congenital infections. The nucleoside analogue ganciclovir (GCV), which requires initial phosphorylation by the viral UL97 kinase, is the mainstay for treatment. To date, CMV decay kinetics during GCV therapy have not been extensively investigated and its clinical implications not fully appreciated. We measured CMV DNA levels in the blood of 92 solid organ transplant recipients with CMV disease over the initial 21 days of ganciclovir therapy and identified four distinct decay patterns, including a new pattern exhibiting a transient viral rebound (Hump) following initial decline. Since current viral dynamics models were unable to account for this Hump profile, we developed a novel multi-level model, which includes the intracellular role of UL97 in the continued Activation of ganciclovir, that successfully described all the decline patterns observed. Fitting the data allowed us to estimate ganciclovir effectiveness in vivo (mean 92%), infected cell half-life (mean 0.7 days), and other viral dynamics parameters that determine which of the four kinetic patterns will ensue. An important clinical implication of our results is that the virological efficacy of GCV operates over a broad dose range. The model also raises the possibility that GCV can drive replication to a new lower steady state but ultimately cannot fully eradicate it. This model is likely to be generalizable to other anti-CMV nucleoside analogs that require Activation by viral enzymes such as UL97 or its homologues.
Chahrazade El Amri - One of the best experts on this subject based on the ideXlab platform.
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human and viral nucleoside nucleotide kinases involved in antiviral Drug Activation structural and catalytic properties
Antiviral Research, 2010Co-Authors: Dominique Devillebonne, Chahrazade El Amri, Philippe Meyer, Yuxing Chen, Luigi A Agrofoglio, Joel JaninAbstract:Abstract Antiviral nucleoside and nucleotide analogs, essential for the treatment of viral infections in the absence of efficient vaccines, are proDrug forms of the active compounds that target the viral DNA polymerase or reverse transcriptase. The Activation process requires several successive phosphorylation steps catalyzed by different kinases, which are present in the host cell or encoded by some of the viruses. These Activation reactions often are rate-limiting steps and are thus open to improvement. We review here the structural and enzymatic properties of the enzymes that carry out the Activation of analogs used in therapy against human immunodeficiency virus and against DNA viruses such as hepatitis B, herpes and poxviruses. Four major classes of Drugs are considered: thymidine analogs, non-natural l -nucleosides, acyclic nucleoside analogs and acyclic nucleoside phosphonate analogs. Their efficiency as Drugs depends both on the low specificity of the viral polymerase that allows their incorporation into DNA, but also on the ability of human/viral kinases to provide the activated triphosphate active forms at a high concentration at the right place. Two distinct modes of action are considered, depending on the origin of the kinase (human or viral). If the human kinases are house-keeping enzymes that belong to the metabolic salvage pathway, herpes and poxviruses encode for related enzymes. The structures, substrate specificities and catalytic properties of each of these kinases are discussed in relation to Drug Activation.
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Human and viral nucleoside/nucleotide kinases involved in antiviral Drug Activation: structural and catalytic properties.
Antiviral research, 2010Co-Authors: Dominique Deville-bonne, Chahrazade El Amri, Philippe Meyer, Yuxing Chen, Luigi A Agrofoglio, Joel JaninAbstract:Abstract Antiviral nucleoside and nucleotide analogs, essential for the treatment of viral infections in the absence of efficient vaccines, are proDrug forms of the active compounds that target the viral DNA polymerase or reverse transcriptase. The Activation process requires several successive phosphorylation steps catalyzed by different kinases, which are present in the host cell or encoded by some of the viruses. These Activation reactions often are rate-limiting steps and are thus open to improvement. We review here the structural and enzymatic properties of the enzymes that carry out the Activation of analogs used in therapy against human immunodeficiency virus and against DNA viruses such as hepatitis B, herpes and poxviruses. Four major classes of Drugs are considered: thymidine analogs, non-natural l -nucleosides, acyclic nucleoside analogs and acyclic nucleoside phosphonate analogs. Their efficiency as Drugs depends both on the low specificity of the viral polymerase that allows their incorporation into DNA, but also on the ability of human/viral kinases to provide the activated triphosphate active forms at a high concentration at the right place. Two distinct modes of action are considered, depending on the origin of the kinase (human or viral). If the human kinases are house-keeping enzymes that belong to the metabolic salvage pathway, herpes and poxviruses encode for related enzymes. The structures, substrate specificities and catalytic properties of each of these kinases are discussed in relation to Drug Activation.
Luigi A Agrofoglio - One of the best experts on this subject based on the ideXlab platform.
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human and viral nucleoside nucleotide kinases involved in antiviral Drug Activation structural and catalytic properties
Antiviral Research, 2010Co-Authors: Dominique Devillebonne, Chahrazade El Amri, Philippe Meyer, Yuxing Chen, Luigi A Agrofoglio, Joel JaninAbstract:Abstract Antiviral nucleoside and nucleotide analogs, essential for the treatment of viral infections in the absence of efficient vaccines, are proDrug forms of the active compounds that target the viral DNA polymerase or reverse transcriptase. The Activation process requires several successive phosphorylation steps catalyzed by different kinases, which are present in the host cell or encoded by some of the viruses. These Activation reactions often are rate-limiting steps and are thus open to improvement. We review here the structural and enzymatic properties of the enzymes that carry out the Activation of analogs used in therapy against human immunodeficiency virus and against DNA viruses such as hepatitis B, herpes and poxviruses. Four major classes of Drugs are considered: thymidine analogs, non-natural l -nucleosides, acyclic nucleoside analogs and acyclic nucleoside phosphonate analogs. Their efficiency as Drugs depends both on the low specificity of the viral polymerase that allows their incorporation into DNA, but also on the ability of human/viral kinases to provide the activated triphosphate active forms at a high concentration at the right place. Two distinct modes of action are considered, depending on the origin of the kinase (human or viral). If the human kinases are house-keeping enzymes that belong to the metabolic salvage pathway, herpes and poxviruses encode for related enzymes. The structures, substrate specificities and catalytic properties of each of these kinases are discussed in relation to Drug Activation.
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Human and viral nucleoside/nucleotide kinases involved in antiviral Drug Activation: structural and catalytic properties.
Antiviral research, 2010Co-Authors: Dominique Deville-bonne, Chahrazade El Amri, Philippe Meyer, Yuxing Chen, Luigi A Agrofoglio, Joel JaninAbstract:Abstract Antiviral nucleoside and nucleotide analogs, essential for the treatment of viral infections in the absence of efficient vaccines, are proDrug forms of the active compounds that target the viral DNA polymerase or reverse transcriptase. The Activation process requires several successive phosphorylation steps catalyzed by different kinases, which are present in the host cell or encoded by some of the viruses. These Activation reactions often are rate-limiting steps and are thus open to improvement. We review here the structural and enzymatic properties of the enzymes that carry out the Activation of analogs used in therapy against human immunodeficiency virus and against DNA viruses such as hepatitis B, herpes and poxviruses. Four major classes of Drugs are considered: thymidine analogs, non-natural l -nucleosides, acyclic nucleoside analogs and acyclic nucleoside phosphonate analogs. Their efficiency as Drugs depends both on the low specificity of the viral polymerase that allows their incorporation into DNA, but also on the ability of human/viral kinases to provide the activated triphosphate active forms at a high concentration at the right place. Two distinct modes of action are considered, depending on the origin of the kinase (human or viral). If the human kinases are house-keeping enzymes that belong to the metabolic salvage pathway, herpes and poxviruses encode for related enzymes. The structures, substrate specificities and catalytic properties of each of these kinases are discussed in relation to Drug Activation.
Yuxing Chen - One of the best experts on this subject based on the ideXlab platform.
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human and viral nucleoside nucleotide kinases involved in antiviral Drug Activation structural and catalytic properties
Antiviral Research, 2010Co-Authors: Dominique Devillebonne, Chahrazade El Amri, Philippe Meyer, Yuxing Chen, Luigi A Agrofoglio, Joel JaninAbstract:Abstract Antiviral nucleoside and nucleotide analogs, essential for the treatment of viral infections in the absence of efficient vaccines, are proDrug forms of the active compounds that target the viral DNA polymerase or reverse transcriptase. The Activation process requires several successive phosphorylation steps catalyzed by different kinases, which are present in the host cell or encoded by some of the viruses. These Activation reactions often are rate-limiting steps and are thus open to improvement. We review here the structural and enzymatic properties of the enzymes that carry out the Activation of analogs used in therapy against human immunodeficiency virus and against DNA viruses such as hepatitis B, herpes and poxviruses. Four major classes of Drugs are considered: thymidine analogs, non-natural l -nucleosides, acyclic nucleoside analogs and acyclic nucleoside phosphonate analogs. Their efficiency as Drugs depends both on the low specificity of the viral polymerase that allows their incorporation into DNA, but also on the ability of human/viral kinases to provide the activated triphosphate active forms at a high concentration at the right place. Two distinct modes of action are considered, depending on the origin of the kinase (human or viral). If the human kinases are house-keeping enzymes that belong to the metabolic salvage pathway, herpes and poxviruses encode for related enzymes. The structures, substrate specificities and catalytic properties of each of these kinases are discussed in relation to Drug Activation.
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Human and viral nucleoside/nucleotide kinases involved in antiviral Drug Activation: structural and catalytic properties.
Antiviral research, 2010Co-Authors: Dominique Deville-bonne, Chahrazade El Amri, Philippe Meyer, Yuxing Chen, Luigi A Agrofoglio, Joel JaninAbstract:Abstract Antiviral nucleoside and nucleotide analogs, essential for the treatment of viral infections in the absence of efficient vaccines, are proDrug forms of the active compounds that target the viral DNA polymerase or reverse transcriptase. The Activation process requires several successive phosphorylation steps catalyzed by different kinases, which are present in the host cell or encoded by some of the viruses. These Activation reactions often are rate-limiting steps and are thus open to improvement. We review here the structural and enzymatic properties of the enzymes that carry out the Activation of analogs used in therapy against human immunodeficiency virus and against DNA viruses such as hepatitis B, herpes and poxviruses. Four major classes of Drugs are considered: thymidine analogs, non-natural l -nucleosides, acyclic nucleoside analogs and acyclic nucleoside phosphonate analogs. Their efficiency as Drugs depends both on the low specificity of the viral polymerase that allows their incorporation into DNA, but also on the ability of human/viral kinases to provide the activated triphosphate active forms at a high concentration at the right place. Two distinct modes of action are considered, depending on the origin of the kinase (human or viral). If the human kinases are house-keeping enzymes that belong to the metabolic salvage pathway, herpes and poxviruses encode for related enzymes. The structures, substrate specificities and catalytic properties of each of these kinases are discussed in relation to Drug Activation.
