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Influenza Nucleoprotein Interactions As Potential Antiviral Targets
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Book Synopsis Influenza Nucleoprotein Interactions as Potential Antiviral Targets by : Abel Sanchez
Download or read book Influenza Nucleoprotein Interactions as Potential Antiviral Targets written by Abel Sanchez and published by . This book was released on 2011 with total page 156 pages. Available in PDF, EPUB and Kindle. Book excerpt: The purpose of this research was to investigate the Nucleoprotein (NP) RNA dependent RNA polymerase (RdRP) interaction by identifying and characterizing a NP mutant which maintains RNA binding but is unable to interact with the viral polymerase complex. Influenza poses a threat to human health and is a burden on the global economy. Influenza is caused by influenza virus which contains a segmented RNA genome, resulting in rapid evolution and emergence of new influenza subtypes which lead to pandemics.
Book Synopsis Identification of Cellular Proteases Involved in Influenza A Virus Replication by : Mable Hagan
Download or read book Identification of Cellular Proteases Involved in Influenza A Virus Replication written by Mable Hagan and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Influenza viruses circulate worldwide and are a serious public health concern, causing annual epidemics of human respiratory tract infections. Reassortment of gene segments between different strains of influenza can generate new pandemic strains, like the 2009 H1N1 pandemic and the current H7N9 avian influenza virus. Vaccines are the most effective option to limit the impact of a pandemic, however preparation of a new vaccine takes months. Antiviral treatment is recommended until a vaccine is available, however the efficacy of current antivirals is highly susceptible to the development of resistance. These pitfalls prioritize the need to discover new compounds targeting essential functions of the virus. My thesis focuses on the identification of cellular proteases that are required for influenza virus replication to develop as potential antiviral targets. Proteolytic cleavage of influenza virus hemagglutinin (HA) is essential for infectivity. Although several cellular proteases have shown HA cleaving activity, these proteases demonstrate significant variation in the cleavage efficiency across the HA subtypes found in human and avian viruses, including some subtypes that are not cleaved by any of these proteases. This work aimed to identify novel cellular proteases that are involved in HA activation by using a human protease siRNA library to screen Caco2 cells infected with a seasonal GFP-expressing influenza virus. Potential proteases identified were validated using wild-type influenza viruses of different subtypes. The most promising protease candidate identified was MASP1, and a MASP1 stably-knocked down Caco2 (MASP1-KD) cell line was generated. MASP1 was shown to be essential for efficient replication of a broad range of influenza virus subtypes. Assessment of where MASP1 fits into the influenza virus life cycle revealed that MASP1 most likely is involved in later stages of viral replication. Comparison of the proteomic profiles between Caco2 and MASP1-KD cells further revealed possible cellular pathway interactions that MASP1 may be involved in. The discovery of a new role for MASP1 in the replication of influenza viruses, and possibly other viral families, provides a strong foundation for future studies to evaluate the effectiveness of MASP1 therapeutics and expands our knowledge of virus and host biology.
Book Synopsis DEVELOPMENT OF ANTIVIRAL AGENT by : Shuofeng Yuan
Download or read book DEVELOPMENT OF ANTIVIRAL AGENT written by Shuofeng Yuan and published by Open Dissertation Press. This book was released on 2017-01-26 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Development of Antiviral Agents Targeting the RNA Polymerase of Influenza Virus" by Shuofeng, Yuan, 袁碩峰, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: The rapid mutability of influenza virus in conjunction with genomic reassortment between viral strains promotes the virus' ability to evade vaccines and to become resistant to antiviral drugs. Therefore, novel anti-influenza therapeutics utilizing new targets and creative strategies are essential. The RNA-dependent RNA polymerase of the virus consists of PA, PB1, and PB2 subunits. Biological and structural investigations of the functional domains of these subunits have broadened the target reservoir for drug screening. With the wealth of knowledge from these studies, identification of small-molecule inhibitors that specifically disrupt the polymerase assembly or abrogate polymerase activities has emerged as an innovative and promising approach. In an attempt to facilitate the discovery of antiviral agents that target viral polymerase, isolated functional domains such as the PA endonuclease domain, the PB2 cap-binding domain, and the PA-PB1 interaction domains were expressed as screening targets. Based on the biochemical and structural properties of individual targets, a variety of platforms were established for the effective screening of inhibitors, including systematic evolution of ligands by exponential enrichment (SELEX), fluorescence resonance energy transfer (FRET) assay, fluorescence polarization (FP) assay, and enzyme-linked immunosorbent assay (ELISA). The antiviral efficacies of selected inhibitors were examined in vitro and in vivo, followed by verification of their antiviral mechanisms. Clinical merits of selected inhibitors were further evaluated, focusing mainly on their cross-protection abilities among influenza virus subtypes and their potential synergetic antiviral effects when used in combination with other drugs. A number of small-molecule compounds, i.e. PA-30, ANA-0, PB2-19, PAC-3 and ANA-1, together with the aptamer PAN-2, were identified as potent inhibitors against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9, and H9N2, in Madin-Darby canine kidney (MDCK) cell cultures. The intranasal administration of the identified compounds enhanced survival rates and reduced lung viral loads in BALB/c mice infected with H1N1 virus. The docking analyses predicted the compounds targeting PA or PB2 interacted with enzyme active sites to abolish endonuclease or cap-binding activity of the polymerase, whereas the compound targeting the PA-PB1 interaction likely induced configurational changes that impeded polymerase assembly. In addition, the combined treatment of zanamivir with the PA- or PB2-targeted compounds exerted synergistic antiviral effects in vitro. This study underscores the medical importance of polymerase functional domains as druggable targets, which may be due to the fact that these targeted areas are not only highly conserved among virus subtypes but also key to viral fitness. The identified antivirals exhibit substantial promise for clinical applications and provide new additions to the arsenal of drugs that are already used for chemoprophylaxis and treatment of influenza. Importantly, the established screening platforms for PA endonuclease inhibitors, PB2 cap-binding inhibitors, and PA-PB1 interaction disrupters should advance the development of a category of anti-influenza drugs that target viral polymerase. DOI: 10.5353/th_b5699888 Subjects: Antiviral agents RNA po
Book Synopsis The Threat of Pandemic Influenza by : Institute of Medicine
Download or read book The Threat of Pandemic Influenza written by Institute of Medicine and published by National Academies Press. This book was released on 2005-04-09 with total page 431 pages. Available in PDF, EPUB and Kindle. Book excerpt: Public health officials and organizations around the world remain on high alert because of increasing concerns about the prospect of an influenza pandemic, which many experts believe to be inevitable. Moreover, recent problems with the availability and strain-specificity of vaccine for annual flu epidemics in some countries and the rise of pandemic strains of avian flu in disparate geographic regions have alarmed experts about the world's ability to prevent or contain a human pandemic. The workshop summary, The Threat of Pandemic Influenza: Are We Ready? addresses these urgent concerns. The report describes what steps the United States and other countries have taken thus far to prepare for the next outbreak of "killer flu." It also looks at gaps in readiness, including hospitals' inability to absorb a surge of patients and many nations' incapacity to monitor and detect flu outbreaks. The report points to the need for international agreements to share flu vaccine and antiviral stockpiles to ensure that the 88 percent of nations that cannot manufacture or stockpile these products have access to them. It chronicles the toll of the H5N1 strain of avian flu currently circulating among poultry in many parts of Asia, which now accounts for the culling of millions of birds and the death of at least 50 persons. And it compares the costs of preparations with the costs of illness and death that could arise during an outbreak.
Book Synopsis Influenza Virology by : Yoshihiro Kawaoka
Download or read book Influenza Virology written by Yoshihiro Kawaoka and published by Horizon Scientific Press. This book was released on 2006 with total page 367 pages. Available in PDF, EPUB and Kindle. Book excerpt: World renowned scientists critically review the most important issues in this rapidly expanding field.
Book Synopsis Textbook of Influenza by : Robert G. Webster
Download or read book Textbook of Influenza written by Robert G. Webster and published by John Wiley & Sons. This book was released on 2014-01-06 with total page 684 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Textbook of Influenza is a comprehensive resource covering all aspects of influenza, from the genetic and molecular biology of the virus through to clinical aspects of the disease and the latest drug developments and treatments. This new edition has been completely revised and reflects the integration of disciplines concerning the emergence, evolution, pathogenesis and control of influenza viruses in the field of human and veterinary public health. Textbook of Influenza examines the lessons learnt from the latest pandemic and provides the current state of knowledge for many yet unresolved issues related to virus origin, spread, pathogenesis and disease severity to better prepare for future pandemics. It covers the background to recent advances in influenza genomics and reverse genetics which have allowed the identification of virus virulence factors and the analysis and reconstruction of influenza viruses such as the 1918 Spanish flu strain. This new edition is divided into eight key sections, containing chapters co-written by international experts from both the clinical and 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 the area of influenza including clinical and basic scientists, immunologists, molecular and structural virologists, public health officials and global pandemic control planners.
Book Synopsis The Domestic and International Impacts of the 2009-H1N1 Influenza A Pandemic by : Institute of Medicine
Download or read book The Domestic and International Impacts of the 2009-H1N1 Influenza A Pandemic written by Institute of Medicine and published by National Academies Press. This book was released on 2010-07-04 with total page 440 pages. Available in PDF, EPUB and Kindle. Book excerpt: In March and early April 2009, a new, swine-origin 2009-H1N1 influenza A virus emerged in Mexico and the United States. During the first few weeks of surveillance, the virus spread by human-to-human transmission worldwide to over 30 countries. On June 11, 2009, the World Health Organization (WHO) raised the worldwide pandemic alert level to Phase 6 in response to the ongoing global spread of the novel influenza A (H1N1) virus. By October 30, 2009, the H1N1 influenza A had spread to 191 countries and resulted in 5,700 fatalities. A national emergency was declared in the United States and the swine flu joined SARS and the avian flu as pandemics of the 21st century. Vaccination is currently available, but in limited supply, and with a 60 percent effectiveness rate against the virus. The story of how this new influenza virus spread out of Mexico to other parts of North America and then on to Europe, the Far East, and now Australia and the Pacific Rim countries has its origins in the global interconnectedness of travel, trade, and tourism. Given the rapid spread of the virus, the international scientific, public health, security, and policy communities had to mobilize quickly to characterize this unique virus and address its potential effects. The World Health Organization and Centers for Disease Control have played critical roles in the surveillance, detection and responses to the H1N1 virus. The Domestic and International Impacts of the 2009-H1N1 Influenza A Pandemic: Global Challenges, Global Solutions aimed to examine the evolutionary origins of the H1N1 virus and evaluate its potential public health and socioeconomic consequences, while monitoring and mitigating the impact of a fast-moving pandemic. The rapporteurs for this workshop reported on the need for increased and geographically robust global influenza vaccine production capacities; enhanced and sustained interpandemic demand for seasonal influenza vaccines; clear "triggers" for pandemic alert levels; and accelerated research collaboration on new vaccine manufacturing techniques. This book will be an essential guide for healthcare professionals, policymakers, drug manufacturers and investigators.
Book Synopsis Influenza Virus Sialidase - A Drug Discovery Target by : Mark Itzstein
Download or read book Influenza Virus Sialidase - A Drug Discovery Target written by Mark Itzstein and published by Springer Science & Business Media. This book was released on 2011-09-01 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt: Influenza continues to be an ongoing problem despite the existence of vaccines and drugs. Disease outbreaks can occur relatively quickly as witnessed with the recent emergence of the influenza virus A/H1N1 pandemic. The development of new anti-influenza drugs is thus a major challenge. This volume describes all aspects of the virus structure and function relevant to infection. The focus is on drug discovery of inhibitors to the enzyme sialidase, which plays a key role in the infectious lifecycle of the virus. Following an overview of the influenza virus, the haemagglutinin, the interactions with the cell receptors and the enzymology of virus sialidase, recent results in drug design are presented. These include a full coverage of the design, synthesis and evaluation of carbohydrate as well as non-carbohydrate influenza virus sialidase inhibitors. Further reviews of the clinical experience with influenza virus sialidase inhibitors and of the development of resistance to these inhibitor drugs complement the topic.
Book Synopsis Peptide Self-Assembly by : Bradley L. Nilsson
Download or read book Peptide Self-Assembly written by Bradley L. Nilsson and published by Humana. This book was released on 2018-05-10 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume details methods and protocols on b-sheet assemblies and collagen. Divided into three parts chapters focus on expanding use of solid-state NMR as a powerful method to enhance structural understanding of self-assembled peptide materials, methods for the design, synthesis, and application of self-assembled peptide materials, and structural and mechanistic analyses of pathological amyloid systems that provide novel ways to assess function of the various possible aggregates as well to determine how the structure of these materials correlates to function/dysfunction in the biological context. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Peptide Self-Assembly: Methods and Protocols aims to capture modern methods that span the breadth of the exciting and expanding field of peptide self-assembly.
Book Synopsis Viral Molecular Machines by : Michael G. Rossmann
Download or read book Viral Molecular Machines written by Michael G. Rossmann and published by Springer Science & Business Media. This book was released on 2012-02-02 with total page 685 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book will contain a series of solicited chapters that concern with the molecular machines required by viruses to perform various essential functions of virus life cycle. The first three chapters (Introduction, Molecular Machines and Virus Architecture) introduce the reader to the best known molecular machines and to the structure of viruses. The remainder of the book will examine in detail various stages of the viral life cycle. Beginning with the viral entry into a host cell, the book takes the reader through replication of the genome, synthesis and assembly of viral structural components, genome packaging and maturation into an infectious virion. Each chapter will describe the components of the respective machine in molecular or atomic detail, genetic and biochemical analyses, and mechanism. Topics are carefully selected so that the reader is exposed to systems where there is a substantial infusion of new knowledge in recent years, which greatly elevated the fundamental mechanistic understanding of the respective molecular machine. The authors will be encouraged to simplify the detailed knowledge to basic concepts, include provocative new ideas, as well as design colorful graphics, thus making the cutting-edge information accessible to broad audience.
Book Synopsis Antiviral Drug Discovery and Development by : Xinyong Liu
Download or read book Antiviral Drug Discovery and Development written by Xinyong Liu and published by Springer Nature. This book was released on 2021-07-13 with total page 357 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book summarizes state-of-the-art antiviral drug design and discovery approaches starting from natural products to de novo design, and provides a timely update on recently approved antiviral drugs and compounds in advanced clinical development. Special attention is paid to viral infections with a high impact on the world population or highly relevant from the public health perspective (HIV, hepatitis C, influenza virus, etc.). In these chapters, limitations associated with adverse effects and emergence of drug resistance are discussed in detail. In addition to classical antiviral strategies, chapters will be dedicated to discuss the non-classical drug development strategies to block viral infection, for instance, allosteric inhibitors, covalent antiviral agents, or antiviral compounds targeting protein–protein interactions. Finally, current prospects for producing broad-spectrum antiviral inhibitors will be also addressed. The book is distinctive in providing the most recent update in the rapidly evolving field of antiviral therapeutics. Authoritative reviews are written by international scientists well known for their contributions in their topics of research, which makes this book suitable for researchers not only within the antiviral research community but also attractive to a broad audience in the drug discovery field. This book covers molecular structures and biochemical mechanisms mediating the antiviral effects, while discussing various ligand design strategies, which include traditional medicinal chemistry, computational chemistry, and chemical biology approaches. The book provides a comprehensive review of antiviral drug discovery and development approaches, particularly focusing on current innovations and future trends.
Book Synopsis Current Issues in Molecular Virology by : Victor Romanowski
Download or read book Current Issues in Molecular Virology written by Victor Romanowski and published by BoD – Books on Demand. This book was released on 2013-11-20 with total page 297 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a collection of chapters dealing with examples of RNA and DNA viruses, and issues such as how these gene packages have learnt to take advantage of their hosts, molecular recognition events that hosts may use to counterattack the viruses, and how researchers have developed strategies to use viruses or their parts as tools for different purposes.
Download or read book Flu written by Gina Kolata and published by Farrar, Straus and Giroux. This book was released on 2011-04-01 with total page 378 pages. Available in PDF, EPUB and Kindle. Book excerpt: Veteran journalist Gina Kolata's Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It presents a fascinating look at true story of the world's deadliest disease. In 1918, the Great Flu Epidemic felled the young and healthy virtually overnight. An estimated forty million people died as the epidemic raged. Children were left orphaned and families were devastated. As many American soldiers were killed by the 1918 flu as were killed in battle during World War I. And no area of the globe was safe. Eskimos living in remote outposts in the frozen tundra were sickened and killed by the flu in such numbers that entire villages were wiped out. Scientists have recently rediscovered shards of the flu virus frozen in Alaska and preserved in scraps of tissue in a government warehouse. Gina Kolata, an acclaimed reporter for The New York Times, unravels the mystery of this lethal virus with the high drama of a great adventure story. Delving into the history of the flu and previous epidemics, detailing the science and the latest understanding of this mortal disease, Kolata addresses the prospects for a great epidemic recurring, and, most important, what can be done to prevent it.
Book Synopsis Animal Influenza by : David E. Swayne
Download or read book Animal Influenza written by David E. Swayne and published by John Wiley & Sons. This book was released on 2016-10-14 with total page 755 pages. Available in PDF, EPUB and Kindle. Book excerpt: Animal Influenza, Second Edition is a comprehensive text on animal influenza. Organized by species, coverage includes avian, swine, equine and mammals, with each section including data on influenza viruses, the infection and disease they cause, and strategies used in control. Covers the full range of topics within avian, swine, equine and mammalian influenzas in one comprehensive and authoritative text Provides a summarization of peer-reviewed and empirical data on influenza viruses, the infection, and diseases they cause Discusses strategies used in control of the disease Leading experts are drawn together to provide an international and multi-disciplinary perspective Fuses latest developments in basic scientific research with practical guidance on management of the disease
Book Synopsis Fortnightly Review.; 31 by : Anonymous
Download or read book Fortnightly Review.; 31 written by Anonymous and published by Legare Street Press. This book was released on 2021-09-09 with total page 504 pages. Available in PDF, EPUB and Kindle. Book excerpt: This work has been selected by scholars as being culturally important and is part of the knowledge base of civilization as we know it. This work is in the public domain in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. To ensure a quality reading experience, this work has been proofread and republished using a format that seamlessly blends the original graphical elements with text in an easy-to-read typeface. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant.
Book Synopsis Mucosal Vaccines by : Hiroshi Kiyono
Download or read book Mucosal Vaccines written by Hiroshi Kiyono and published by Elsevier. This book was released on 1996-10-23 with total page 501 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive, authoritative treatise covers all aspects of mucosal vaccines including their development, mechanisms of action, molecular/cellular aspects, and practical applications. The contributing authors and editors of this one-of-a-kind book are very well known in their respective fields. Mucosal Vaccines is organized in a unique format in which basic, clinical, and practical aspects of the mucosal immune system for vaccine development are described and discussed. This project is endorsed by the Society for Mucosal Immunology. Provides the latest views on mucosal vaccines Applies basic principles to the development of new vaccines Links basic, clinical, and practical aspects of mucosal vaccines to different infectious diseases Unique and user-friendly organization
Book Synopsis Emerging Viral Diseases by : Institute of Medicine
Download or read book Emerging Viral Diseases written by Institute of Medicine and published by National Academies Press. This book was released on 2015-03-19 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the past half century, deadly disease outbreaks caused by novel viruses of animal origin - Nipah virus in Malaysia, Hendra virus in Australia, Hantavirus in the United States, Ebola virus in Africa, along with HIV (human immunodeficiency virus), several influenza subtypes, and the SARS (sudden acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses - have underscored the urgency of understanding factors influencing viral disease emergence and spread. Emerging Viral Diseases is the summary of a public workshop hosted in March 2014 to examine factors driving the appearance, establishment, and spread of emerging, re-emerging and novel viral diseases; the global health and economic impacts of recently emerging and novel viral diseases in humans; and the scientific and policy approaches to improving domestic and international capacity to detect and respond to global outbreaks of infectious disease. This report is a record of the presentations and discussion of the event.
