Hepatitis C Virus From Molecular Virology To Antiviral Therapy

Hepatitis C virus (HCV), a major causative agent of chronic liver disease, is spread throughout the world and around 170 million people are persistently infected. In this volume, world-leading experts in the field of HCV research have compiled the most recent scientific advances to provide a comprehensive and very timely overview of the various facets of HCV. The book starts with a discussion of the possible origin of HCV and its spread among the human population. The focus of the subsequent chapters is on available cell culture and in vivo models before shifting to the molecular and cellular principles underlying the viral replication cycle. These chapters are complemented by insightful descriptions of the innate and adaptive immune responses to HCV as well as the virus-associated pathogenesis. Finally, the development of antiviral therapies, which is closely linked with progress in basic research, and the implementation of those therapies into present and future daily clinical practice are highlighted.

Hepatitis C is a liver disease caused by the hepatitis C virus (HCV) and infects approximately 75 million individuals worldwide. It is also one of the major causes of liver cancer and liver transplants. The elucidation of the HCV genome, and the development of a whole cell system to study the virus spurred the search for novel direct acting antiviral drugs to cure this disease. This global effort culminated in the development of direct acting antiviral drugs that led to cure rates approaching 100% in all patient populations after only 8-12 weeks of therapy. These efforts resulted in one of the greatest achievements in public health and provides the potential for eliminating HCV as a major disease worldwide. This volume is aimed at a broad audience of academic and industrial scientists interested in the discovery and development of drugs to treat viral diseases and those interested in reading about one of the most unique accomplishments in biomedical research. The volume will provide a one of a kind reference work that highlights the many efforts, from the discovery of the HCV virus, to the invention of breakthrough medicines and their use in the real world to cure patients. It is the companion book to the volume "HCV: The Journey from Discovery to a Cure - Volume II".

This book covers various aspects of Molecular Virology. The first chapter discusses HIV-1 reservoirs and latency and how these twin phenomena have remained a challenge to eradication. Aspects regarding the molecular evolution of hepatitis viruses including their genetic diversities with implications for vaccine development are treated in the second chapter. Metabolic disorders that are a consequence of hepatitis C virus infection are discussed in the succeeding chapter. The following two chapters discuss influenza C virus and the applications of viral vectors in therapeutic research. Avian influenza is handled in the sixth chapter and the therapeutic potential of belladonna-200 against japanese encephalitis virus infection is discussed in the succeeding chapter. The last two chapters discuss baculoviruses and their interaction with polydnaviruses. Researchers, lecturers and students will find this book an indispensable companion.

The hepatitis C virus (HCV) is a significant public health problem of international importance. HCV is capable of establishing chronic infections resulting in progressive liver damage and other problems. Current drug therapies are ineffective, highlighting the need for better antiviral drugs. Recent research in HCV genetics and molecular biology have led to significant advances in our understanding of the life cycle of this important pathogen and may ultimately lead to better antiviral strategies. The editors of this book have recruited experts from around the world to produce a timely and well-compiled review of current HCV research, with an emphasis on antiviral drug development. The chapters provide in-depth reviews of the most critical areas of research. Topics include: the HCV life cycle * HCV assays * HCV resources * HCV databases * HCV infection systems * models of hepatitis C infections * overview of the drug pipeline * clinical trial design * clinical virology and drug development * NS3 protease inhibitors * NS3-NS4A complex inhibitors * NS3 helicase inhibitors * NS4B targets and inhibitors * NS5A inhibitors * nucleoside inhibitors * NS5B polymerase inhibitors * glycoprotein-dependent entry * host cell targets and inhibitors * innate immunity for HCV antiviral therapy.

This volume is composed of chapters that review important fundamental aspects of HCV biology and disease pathogenesis including, for example, the discovery and identification of the HCV genome, early virus-cell interactions including identification of various cellular receptors, HCV gene expression studied using the HCV replicon system, identification and characterization of HCV structural- and non-structural HCV proteins, HCV replication in cultured cells, and host factors involved in viral replication. This volume also contains chapters dealing with immunity to HCV infection and pathogenesis. This is particularly important in understanding hepatitis C because HCV infection alone is not cell lytic. Mechanisms underlying the persistent nature of HCV infection are also discussed in these chapters. Many of the authors published articles that were listed among the “top 10 papers” published in the 24 years since HCV was discovered in 1989. Their citations are above 1,000 (Web of Science). The authors describe the background and significance of their contributions to the field in the context of findings from other research groups.

Chronic viral hepatitis has emerged as one of the most common causes of disease and death worldwide. Because of their unique modes of replication and intimate association with the host immune system, hepatitis B virus (HBV) and hepatitis C virus (HCV) pose challenging problems to scientists in basic and applied research as well as to clinicians engaged in disease management. Although approved antiviral therapy is available for chronic HBV, the emergence of viral resistance provides a rationale for the development of novel chemotherapeutic agents. The lack of a robust cell culture system for HCV replication and a readily accessible small-animal model of HCV infection have hampered the development of antiviral agents for HCV. Neverthe-less, new antiviral agents targeting HCV are now in preclinical and clinical development. This monograph, providing an up-to-date overview of the field of Hepatitis Prevention and Treatment, includes contributions from internationally recognized experts in the field of viral hepatitis, and covers the current state of knowledge and practice regarding the molecular biology, immunology, biochemistry, pharmacology and clinical aspects of chronic HBV and HCV infection. The volume includes salient topics such as: the history and epidemiology of HBV and HCV; recent insights into the molecular mechanisms of viral replication; the host immune response to infection and a discussion of the use (HBV) or potential development (HCV) of vaccines; the current standard of care for chronically-infected patients; and emerging therapies and issues associated with current antiviral treatments. The latest information to researchers and clinicians actively engaged in viral hepatitis research is provided, but also sufficient background and discussion of the literature to benefit the newcomer to the field.

This book introduces readers to Direct Acting Antiviral (DAAs) agents, newly developed drugs to treat chronic hepatitis C virus infection, which have an excellent anti-viral effect on virus replication. These drugs have been developed to enhance the effect of interferon and ribavirin, as the resistant strains against each drug have been described both in vitro and in vivo and the existences of naturally occurring variants have been reported. However, since the combination of different classes of DAAs is sufficient to completely eradicate the virus without the need for interferon or ribavirin, the current treatment regimen does not include interferon. Ribavirin is used in combination with sofosbuvir, a potent polymerase inhibitor, to enhance its antiviral effects. Hepatitis C Virus Treatment offers readers a comprehensive guide to hepatitis C; describing the resistance profiles against these drugs and shedding light on the difficulties involved in DAA therapy and the direction of future treatments, it will equip doctors to understand the essentials of treating the disease. It also describes in detail new and innovative DAA treatments, the effects of the agents, and the characteristics of resistance, providing cutting-edge information not only for hepatologists, but also for researchers, clinical residents, and medical students.

There has been an explosion of both the incidence and medicalknowledge of viral hepatitis over the last two decades. Not only isthe incidence of infection and disease increasing, but newhepatitis viruses have been discovered, as well as the launch ofnew pharmaceutical products. Previously published by Churchill Livingstone, ViralHepatitis by Zuckerman & Thomas was the first comprehensivebook on hepatitis and is recognized as the standardreference text in this field. The new third edition, now published by Blackwell Publishing,addresses the recent advances in diagnosis and treatment withentirely revised and current topics. It covers the entire spectrumof viral hepatitis and has something of interest for everyspecialist. Viral Hepatitis presents the latest thinking from theleading international researchers and clinicians working in thisfield and the Editors are joined by a North American co-Editor forthis edition - Professor Stanley Lemon of the University of Texas,Galveston, TX, USA. This book offers an ideal reference for all healthcareprofessionals involved in the research and patient care of thisdisease.