Viral polymerases : structures, functions and roles as antiviral drug targets /

Detalles Bibliográficos
Clasificación:Libro Electrónico
Otros Autores: Gupta, Satya Prakash (Editor )
Formato: Electrónico eBook
Idioma:Inglés
Publicado: London, United Kingdom : Academic Press, an imprint of Elsevier, [2019]
Temas:
Antiviral agents.
Transferases.
Transferases
Antiviral Agents
Antiviraux.
Transf�erases.
MEDICAL > Pharmacology.
Antiviral agents
Acceso en línea:Texto completo
Tabla de Contenidos:
  • 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 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, 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 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.

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