Viral Polymerases

Book Description :

Viral Polymerases: Structures, Functions and Roles as Antiviral Drug Targets presents in-depth study information on the structure and functions of polymerases and their roles in the lifecycle of viruses, and as drug targets. Viral polymerases constitute a vital component in the lifecycle of many viruses, such as human immunodeficiency virus (HIV), hepatitis viruses, influenza virus, and several others. They are essentially required for the replication of viruses. Thus, the polymerases that can be found in viruses (called viral polymerases) represent favorable targets for the design and development of antiviral drugs. Provides comprehensive, state-of-the-art coverage on virus infections, the virus lifecycle, and mechanisms of polymerase inhibition Analyzes the structure-activity relationships of inhibitors of each viral polymerase Presents a consistent and comprehensive coverage of all aspects of viral polymerases, including structure, function and their role as antiviral drug targets

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The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. More than 270 volumes have been published (all of them still in print) and much of the material is relevant even today--truly an essential publication for researchers in all fields of life sciences. Key Features * Expression, purification, and characterization * Activity assays * Kinetic and screening * Design and analysis of substrates and inhibitors * Molecular and structural characterizations.

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Download Characterization of DNA Polymerase Activities in Mouse Mammary Tumor Virus book written by Rhoda Louise Ashley, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

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Download RNA Tumor Viruses Supplements and appendixes book written by , available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

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Download Structural and Functional Characterization of Escherichia Coli RNA Polymerase Ternary Complexes During Transcript Elongation and Termination book written by Susan Marie Uptain, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

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This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.

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This book provides a review of the multitude of nucleic acid polymerases, including DNA and RNA polymerases from Archea, Bacteria and Eukaryota, mitochondrial and viral polymerases, and other specialized polymerases such as telomerase, template-independent terminal nucleotidyl transferase and RNA self-replication ribozyme. Although many books cover several different types of polymerases, no book so far has attempted to catalog all nucleic acid polymerases. The goal of this book is to be the top reference work for postgraduate students, postdocs, and principle investigators who study polymerases of all varieties. In other words, this book is for polymerase fans by polymerase fans. Nucleic acid polymerases play a fundamental role in genome replication, maintenance, gene expression and regulation. Throughout evolution these enzymes have been pivotal in transforming life towards RNA self-replicating systems as well as into more stable DNA genomes. These enzymes are generally extremely efficient and accurate in RNA transcription and DNA replication and share common kinetic and structural features. How catalysis can be so amazingly fast without loss of specificity is a question that has intrigued researchers for over 60 years. Certain specialized polymerases that play a critical role in cellular metabolism are used for diverse biotechnological applications and are therefore an essential tool for research.

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Download RNA GENETICS DIR VIRUS REPLIC book written by John J. Holland,Paul Ahlquist, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

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Influenza is an RNA virus whose segmented genome is encapsidated into viral ribonucleoprotein complexes (vRNPs). Upon infection, the vRNPs migrate into the nucleus where transcription and replication take place. The vRNPs contain a RNA-dependent RNA polymerase that is responsible for viral transcription and replication. The polymerase is composed of three subunits, PB1, PB2, and PA. PBI has polymerase activity and PB2 is involved in viral transcription. The function of PA is unclear. To help elucidate the role of PA in the viral life cycle, 16 conserved regions of PA were targeted for alanine substitution. A plasmid-based transfection system was used to generate recombinant influenza particles bearing each mutation, which were tested for viral viability and the ability of each mutant polymerase to transcribe and replicate a reporter. Mutations in the N-terminus were not well tolerated and resulted in either non-viable or attenuated viruses. One of the mutants, J10, was capable of RNA synthesis, yet did not create viral particles capable of plaque formation in MDCK cells. Specifically, when compared to wild-type, this mutant synthesized 50+/-7% vRNA, 86+/-12% mRNA, and 128+/-18% cRNA. These levels are compatible with viability, as mutants J8 (27%) and J12 (23%), produced significantly less vRNA than J10, yet were viable by plaque assay. The mRNAs generated from J10 polymerase were found to be translationally-active, and both the mutant protein and its RNA products were appropriately localized in the cytoplasm, where influenza assembly occurs. Nevertheless, J10 failed to generate infectious particles from cells in a plasmid-based influenza assembly assay, and hemagglutinating material from the supernatants of such cells contained little or no nuclease-resistant genomic RNA. These findings suggest that PA has a previously unrecognized role in assembly or release of influenza virions, perhaps influencing core structure or the packaging of vRNAs or other essential components into nascent influenza particles.

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Download Antiviral Mechanisms in the Control of Neoplasia book written by P. Chandra, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

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The basis for the effective treatment and cure of a patient is the rapid diagnosis of the disease and its causative agent, which is based on the analysis of the clinical symptoms coupled with laboratory tests. Although rapid advance ments have been made in the laboratory diagnosis of virus diseases, the neces sary isolation of the causative virus from the clinical specimens is a relatively long procedure. Viruses which integrate into the cellular DNA (such as human immunodeficiency virus, HIV -1, or hepatitis B virus) are difficult to identify by molecular techniques, while viruses which exist in the clinical material in low concentrations are even more formidable to identify. Recently, the application of the polymerase chain reaction (peR) technique developed by K. D. Mullis and detailed in the study by Saiki et al. (1985) led to a revolution in virus diagnosis. The peR technique was rapidly applied to the diagnosis of viruses in clinical material. Volume 1 of Frontiers of Virology provides new information on the advan tages of the use of the peR for the diagnosis of many human disease-causing viruses, as well as on some problems with its use.

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Download Molecular Biology of the Cell book written by Bruce Alberts, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

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The Textbook of Influenza is a comprehensive resourcecovering all aspects of influenza, from the genetic and molecularbiology of the virus through to clinical aspects of the disease andthe latest drug developments and treatments. This new edition hasbeen completely revised and reflects the integration of disciplinesconcerning the emergence, evolution, pathogenesis and control ofinfluenza viruses in the field of human and veterinary publichealth. Textbook of Influenza examines the lessons learnt fromthe latest pandemic and provides the current state of knowledge formany yet unresolved issues related to virus origin, spread,pathogenesis and disease severity to better prepare for futurepandemics. It covers the background to recent advances in influenzagenomics and reverse genetics which have allowed the identificationof virus virulence factors and the analysis and reconstruction ofinfluenza viruses such as the 1918 Spanish flu strain. This new edition is divided into eight key sections, containingchapters co-written by international experts from both the clinicaland scientific communities, covering: • Influenza Perspectives • Structure and Replication • Evolution and Ecology • Epidemiology and Surveillance • Immunology • Vaccines and Vaccine Development • Clinical Aspects and Antivirals • Public Health Textbook of Influenza is for all those working in thearea of influenza including clinical and basic scientists,immunologists, molecular and structural virologists, public healthofficials and global pandemic control planners.

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Genome Stability: From Virus to Human Application, Second Edition, a volume in the Translational Epigenetics series, explores how various species maintain genome stability and genome diversification in response to environmental factors. Here, across thirty-eight chapters, leading researchers provide a deep analysis of genome stability in DNA/RNA viruses, prokaryotes, single cell eukaryotes, lower multicellular eukaryotes, and mammals, examining how epigenetic factors contribute to genome stability and how these species pass memories of encounters to progeny. Topics also include major DNA repair mechanisms, the role of chromatin in genome stability, human diseases associated with genome instability, and genome stability in response to aging. This second edition has been fully revised to address evolving research trends, including CRISPRs/Cas9 genome editing; conventional versus transgenic genome instability; breeding and genetic diseases associated with abnormal DNA repair; RNA and extrachromosomal DNA; cloning, stem cells, and embryo development; programmed genome instability; and conserved and divergent features of repair. This volume is an essential resource for geneticists, epigeneticists, and molecular biologists who are looking to gain a deeper understanding of this rapidly expanding field, and can also be of great use to advanced students who are looking to gain additional expertise in genome stability. A deep analysis of genome stability research from various kingdoms, including epigenetics and transgenerational effects Provides comprehensive coverage of mechanisms utilized by different organisms to maintain genomic stability Contains applications of genome instability research and outcomes for human disease Features all-new chapters on evolving areas of genome stability research, including CRISPRs/Cas9 genome editing, RNA and extrachromosomal DNA, programmed genome instability, and conserved and divergent features of repair

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Download DNA Polymerases book written by , available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

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Download The Biology of RNA tumor Viruses book written by Howard M. Temin, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

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Download Inhibitors of DNA and RNA Polymerases book written by Prem S. Sarin,Robert C. Gallo, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

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Viral pathogens are responsible for a large number of human infections. For example, the Hepatitis C virus (HCV) affects close to 3% of the world's population. There has been significant progress in the therapeutic options available for the treatment of HCV and most of the highly effective existing therapies are a combination of small molecule inhibitors targeting key viral enzymes. One such target is the polymerase, which is a critical component of the viral life cycle. Our work focuses on understanding inhibition of the polymerase by small molecules that bind to pockets outside the active site (i.e. allosteric inhibitors). The first objective of this study is to determine how allosteric inhibitors alter the structural, dynamic and thermodynamic properties of the HCV polymerase so that these small molecules can synergistically inhibit the enzyme. Our second goal is to identify putative allosteric sites in the polymerases of the Dengue (DENV), West Nile (WNV) and Foot-and-mouth Disease (FMDV) viruses. One of the existing challenges in current HCV treatment is that low fidelity of NS5B increases the rate of mutations in the virus. This results in the generation of multiple enzyme variants and makes it difficult to target the enzyme with single inhibitors. In contrast, for DENV, WNV and FMDV one of the major hurdles is lack of biochemical and structural data that can help steer more structure-based drug discovery efforts. Results from our studies of the HCV polymerase suggest that allosteric inhibitors from nonoverlapping sites can bind simultaneously and synergistically modulate the enzyme conformation and free energy landscape. This work provides the first molecular descriptions of mechanisms underlying enhanced inhibition of the HCV polymerase. We used validated HCV allosteric sites as targets to evaluate several ligand binding site predictor tools and used the best tool to identify novel putative allosteric pockets in the DENV, WNV and FMDV polymerases. The identified sites displayed structural and/or chemical similarities with two of the NS5B validated allosteric pockets. Our approach provides an economic and faster means to facilitate an essential step of drug discovery (i.e. binding site identification), which is critical for infections with limited therapeutic options.

Book Description :

Essential Human Virology is written for the undergraduate level with case studies integrated into each chapter. The structure and classification of viruses will be covered, as well as virus transmission and virus replication strategies based upon type of viral nucleic acid. Several chapters will focus on notable and recognizable viruses and the diseases caused by them, including influenza, HIV, hepatitis viruses, poliovirus, herpesviruses, and emerging and dangerous viruses. Additionally, how viruses cause disease, or pathogenesis, will be highlighted during the discussion of each virus family, and a chapter on the immune response to viruses will be included. Further, research laboratory assays and viral diagnosis assays will be discussed, as will vaccines, anti-viral drugs, gene therapy, and the beneficial uses of viruses. By focusing on general virology principles, current and future technologies, familiar human viruses, and the effects of these viruses on humans, this textbook will provide a solid foundation in virology while keeping the interest of undergraduate students. Focuses on the human diseases and cellular pathology that viruses cause Highlights current and cutting-edge technology and associated issues Presents real case studies and current news highlights in each chapter Features dynamic illustrations, chapter assessment questions, key terms, and summary of concepts, as well as an instructor website with lecture slides, test bank, and recommended activities

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Download Polymerase Chain Reaction Detection and Seminal Shedding of Bluetongue Virus in Sheep book written by Geoffrey Yoshito Akita, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.