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Record Nr. |
UNINA9910583019503321 |
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Titolo |
Viral polymerases : structures, functions and roles as antiviral drug targets / / edited by Satya P. Gupta |
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Pubbl/distr/stampa |
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London, United Kingdom : , : Academic Press, An imprint of Elsevier, , [2019] |
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©2019 |
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ISBN |
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0-12-815423-3 |
0-12-815422-5 |
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Descrizione fisica |
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1 online resource (498 pages) |
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Disciplina |
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Soggetti |
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Antiviral agents |
Transferases |
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Lingua di pubblicazione |
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Formato |
Materiale a stampa |
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Livello bibliografico |
Monografia |
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Note generali |
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Nota di contenuto |
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Front Cover -- Viral Polymerases -- Copyright Page -- Contents -- List of Contributors -- Preface -- 1 RNA-Dependent RNA Polymerases and Their Emerging Roles in Antiviral Therapy -- 1.1 Introduction -- 1.2 RNA Polymerase -- 1.2.1 DNA-Dependent RNA Polymerases -- 1.2.2 RNA-Dependent RNA Polymerases -- 1.3 Structure of Viral RNA-Dependent RNA Polymerases -- 1.3.1 Structural Flexibility -- 1.3.2 Divalent Metal Ions -- 1.4 Mechanism of Enzyme Action -- 1.4.1 Two Metal Ion Mechanism -- 1.4.2 Initiation of RNA Synthesis -- 1.4.2.1 De Novo Initiation Mechanism -- 1.4.2.2 Primer-Dependent Initiation -- 1.5 Structures of Different Viral RdRPs -- 1.5.1 Hepatitis C Virus -- 1.5.2 Poliovirus -- 1.5.3 Influenza A Virus -- 1.5.3.1 Polymerase Basic 1 Subdomain -- 1.5.3.2 Polymerase Basic 2 Subdomain -- 1.5.3.3 Polymerase Acidic Subdomain -- 1.5.4 Dengue Virus -- 1.5.5 Zika Virus -- 1.5.6 Japanese Encephalitis Virus -- 1.5.7 Human Rhinoviruses -- 1.6 Enzyme-Ligand Interaction Strategies (Drug Design and Development) -- 1.7 Synthetic Inhibitors of RdRPs -- 1.7.1 Nucleoside Inhibitors -- 1.7.1.1 Purine Nucleoside Inhibitors -- 1.7.1.2 Pyrimidine Nucleoside Inhibitors -- 1.7.1.3 Miscellaneous Nucleoside Inhibitors -- 1.7.2 Nonnucleoside Inhibitors -- 1.7.2.1 Active Site Inhibitors -- 1.7.2.2 Allosteric Site Inhibitors -- 1.7.2.2.1 Anthranilic Acid |
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Derivatives -- 1.7.2.2.2 Benzimidazole Derivatives -- 1.7.2.2.3 Benzothiadiazine Derivatives -- 1.7.2.2.4 Indole Derivatives -- 1.7.2.2.5 Proline Sulfonamide Derivatives -- 1.7.2.2.6 Pyrrolidine Diacid Derivatives -- 1.7.2.2.7 Pyridobenzothiazole Derivatives -- 1.7.2.3 Miscellaneous -- 1.8 Conclusion -- 1.9 Future Prospective -- References -- 2 Structure-Function Relationship of Negative-Stranded Viral RNA Polymerases: Prospectives for Antiviral Therapy -- 2.1 Introduction -- 2.2 Polyprotein Processing. |
2.3 Genome Organization of Polymerase of segmented negative-strand RNA Viruses -- 2.4 Mechanism of Capping by RdRps -- 2.5 Structures of L-Proteins (Polymerases) -- 2.5.1 Structures of SNS RNA Virus L-Proteins (Polymerases) -- 2.5.1.1 La Crosse Orthobunyavirus RNA Polymerase (L-Protein) -- 2.5.1.2 Influenza Virus (H3N2) RNA Polymerase -- 2.5.1.3 Lymphocytic Choriomeningitis Virus RNA Polymerase (L-Protein) -- 2.5.1.4 Avian Influenza Virus (H5N1) RNA Polymerase -- 2.5.2 Structure of NNS RNA Virus L-Proteins (Polymerases) -- 2.6 Activity Assays -- 2.6.1 Mini-Replicon Assay -- 2.6.2 Nuclease Activity and Thermal Stability Assay -- 2.6.3 UV Cross-Linking Assays for Nucleotide Binding -- 2.6.4 Band Shift Assay for RNA Binding -- 2.6.5 Fluorescence-Based Assay -- 2.7 Inhibition Studies -- 2.7.1 Synergistic Action of Favipiravir and Ribavirin -- 2.7.2 Neutral Red Uptake Assay for Assessing Inhibition of Viral Replication by Antiviral Compounds -- 2.7.3 Negative-Strand Viral Replication Inhibition Through Gene Silencing approaches -- 2.7.4 Exploration of Antiviral Agents for Influenza in Clinical Trials -- 2.7.5 Targeting of Viral RNA in Eukaryotic Cells Through Cas9 -- 2.7.6 Novel Sugar-Modified Nucleosides Inhibitors Against Human RSV Polymerase -- 2.8 Conclusion -- References -- Further Reading -- 3 RNA-Dependent RNA Polymerase of Alphaviruses: A Potential Target for the Design of Drugs Against Alphaviruses -- 3.1 Introduction -- 3.2 Genome Structure -- 3.3 Viral Life Cycle -- 3.4 Replication Complexes in Alphavirus -- 3.5 Structure of RNA-Dependent RNA Polymerases -- 3.5.1 Divalent Metal Binding Site -- 3.5.2 Nucleotide Binding Site -- 3.6 Initiation of Replication -- 3.6.1 Primer-Independent Initiation -- 3.6.2 Primer-Dependent Initiation -- 3.7 Polymerase Activity of Alphaviral RdRP -- 3.7.1 Promoter Recognition by the Polymerase -- 3.7.1.1 5' end. |
3.7.1.2 3' end -- 3.7.1.3 SG Promoter -- 3.7.2 Temperature Sensitivity of Polymerase -- 3.7.3 Fidelity of RdRP -- 3.8 Inhibitors Against Replication of Alphaviruses -- 3.9 Conclusions -- References -- 4 DNA-Dependent DNA Polymerases as Drug Targets in Herpesviruses and Poxviruses -- 4.1 Introduction -- 4.2 DNA Viruses: Mechanisms of Genomic DNA Replication -- 4.2.1 Bidirectional and Rolling Circle Replication -- 4.2.2 Single-Stranded DNA Formation Through Strand Displacement Replication -- 4.3 Herpesviruses -- 4.3.1 Types and Classification -- 4.3.2 Herpesvirus DNA Polymerase Structure -- 4.3.3 DNA Polymerase Properties: Processivity and Nucleotide Specificity -- 4.4 Antiviral Drugs Targeting Herpesvirus DNA Polymerases -- 4.4.1 Approved Drugs -- 4.4.2 Resistance to Approved Drugs Targeting Herpesvirus Replication -- 4.4.3 Drugs in Preclinical and Clinical Development -- 4.5 Poxviruses -- 4.5.1 Poxvirus DNA Polymerase -- 4.5.2 Drugs Targeting Poxvirus DNA Polymerases -- 4.6 Conclusions -- References -- 5 Poliovirus Polymerase: An Effective Target for Design and Development of Antipolio Drugs -- 5.1 Introduction -- 5.2 Poliovirus RNA-Dependent RNA Polymerase -- 5.2.1 Structure -- 5.2.1.1 The Palm Subdomain and Its Motifs -- 5.2.1.2 Fingers Subdomain -- 5.2.1.3 Thumb Subdomain -- 5.2.1.3.1 Roles of Subdomains -- 5.2.1.4 Metal Ions -- 5.2.2 Function -- 5.3 Isolation, |
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Purification, and Characterization of Poliovirus RNA Polymerase -- 5.3.1 Isolation From HeLa cells -- 5.3.2 Recombinant Baculovirus Infected Insect Cells -- 5.3.3 Escherichia coli Transformed With an Expression Plasmid Containing 3Dpol Sequences -- 5.4 RNA-Dependent RNA Polymerase Inhibitors -- 5.5 Conclusions and Future Perspective -- References -- 6 Studies on HIV-1 Polymerase and Its Inhibitors -- 6.1 Introduction -- 6.2 Structure of Reverse Transcriptase. |
6.3 Role and Mechanism of Action of HIV-1 RT -- 6.4 HIV-1 RT Inhibitors -- 6.5 Binding of NNRTIs With the Receptor -- 6.6 Theoretical Studies -- 6.7 RNH Inhibitors -- 6.8 HIV-1 Capsid and Its Role on Reverse Transcription Regulation and Control of Entry of RT Inhibitors -- 6.9 Conclusions -- References -- Further Reading -- 7 A Focus on Ebola Virus Polymerase: Structure, Functions and Antiviral Therapies -- 7.1 Introduction -- 7.1.1 History and Epidemiology -- 7.1.2 Transmission and Pathology -- 7.2 Structure and Genome -- 7.3 Replication -- 7.4 L-Protein -- 7.4.1 RNA-Dependent RNA Polymerase Domain -- 7.4.2 Capping Domain -- 7.4.3 Methyl Transferase Domain -- 7.4.4 Connector and C-Terminal Domains -- 7.4.5 Domain Organization -- 7.4.6 L-Protein in Virus Replication -- 7.5 Antiviral Strategies -- 7.5.1 Brincidofovir (CMX-001) -- 7.5.2 Lamivudine (BCH-189) -- 7.5.3 Favipiravir (T-705) -- 7.5.4 Immucillin A (BCX4430) -- 7.5.5 The FGI (Functional Genetics Inc.) Compounds -- 7.5.6 Neplanocin A (3-deazaneplanocin A) -- 7.5.7 Bioinformatics Approach to Drug Discovery -- 7.6 Ebola Vaccine -- 7.7 Conclusions -- References -- 8 Hepatitis C Virus NS5B RNA-Dependent RNA Polymerase Inhibitor: An Integral Part of HCV Antiviral Therapy -- 8.1 Introduction -- 8.2 The HCV Genome and Viral Replication -- 8.3 Development of HCV-Specific DAA drugs Targeting the NS3 Protease -- 8.4 Development of HCV-Specific DAA drugs Targeting NS5A -- 8.5 Structural and Functional Studies of HCV RNA Polymerase -- 8.6 Initiation of HCV Replication by NS5B Polymerase -- 8.7 Direct-Acting Antivirals Targeting the HCV RNA Polymerase -- 8.7.1 Nucleos(t)ide Inhibitors -- 8.7.2 Nonnucleos(t)ide Inhibitors -- 8.7.2.1 Thumb 1 inhibitors -- 8.7.2.2 Thumb 2 Inhibitors -- 8.7.2.3 Palm 1 Inhibitors -- 8.7.2.4 Palm 2 Inhibitors -- 8.8 Conclusions -- Acknowledgments -- References -- Further Reading. |
9 HBV Polymerase as a Target for Development of Anti-HBV Drugs -- 9.1 Introduction -- 9.2 Structure and Biology of HBV -- 9.2.1 Structure -- 9.2.2 Genome -- 9.2.2.1 Size of Genome -- 9.2.2.2 Encoding -- 9.2.2.3 Genotypes -- 9.3 Life Cycle of HBV -- 9.3.1 Attachment -- 9.3.2 Penetration -- 9.3.3 Uncoating -- 9.3.4 Replication -- 9.3.5 Assembly -- 9.3.6 Release -- 9.4 Structure of HBV Polymerase -- 9.4.1 TP Domain -- 9.4.2 Spacer Domain -- 9.4.3 RT Domain -- 9.4.4 RNase H Domain -- 9.5 Multiple Roles of HBV Polymerase -- 9.6 A Potential Target for Anti-HBV Drugs -- 9.6.1 HBV Mutants -- 9.7 Need for New Drugs -- 9.7.1 Sites of Action for New Drugs -- 9.8 Present Status of Drugs Used Against HBV -- 9.8.1 Rational Synthetic Drugs -- 9.8.2 Empirical Indigenous Drugs -- 9.8.2.1 Choices -- 9.9 Recent Studies on HP Inhibitors -- 9.10 Conclusions -- Acknowledgment -- References -- Further Reading -- 10 Polymerases of Coronaviruses: Structure, Function, and Inhibitors -- 10.1 Introduction -- 10.2 Structure of HCoV RdRP -- 10.3 Function of HCoV RdRP -- 10.4 Clinical Therapies for HCoV Infections -- 10.4.1 Approaches to Identify the Suitable Treatment for SARS -- 10.4.2 RNA-Dependent RNA Polymerase Inhibitors -- 10.4.3 Marketed RdRP Inhibitors -- 10.4.4 Preclinical RdRP Inhibitors -- 10.4.5 Design of SARS-CoV RdRP Inhibitors -- 10.4.5.1 Nucleoside Analog Inhibitors -- 10.4.5.2 Nonnucleoside Analog Inhibitors -- 10.5 Conclusions -- References -- 11 Rhinovirus |
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RNA Polymerase: Structure, Function, and Inhibitors -- 11.1 Introduction -- 11.2 Classification -- 11.3 Structural Features of HRV Polymerase -- 11.3.1 Crystal Structure of HRV 3Dpol -- 11.3.2 Description of Individual Domains -- 11.3.3 Potassium Binding Site -- 11.3.4 Metal Binding at the Active Site -- 11.3.5 Modeling of Duplex Oligonucleotide for HRV 3Dpol -- 11.3.6 Potential Oligomerization Interfaces. |
11.3.7 Conformational Analysis Showing the Flexibility of the Enzyme. |
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