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The antiviral therapeutic area continues to rapidly generate meaningful new chemical entities; for example, for HIV alone more than 25 drugs have been approved, and in the next few years many individual drugs and single tablet regimens will be approved for the treatment of hepatitis C virus infection. The increasing success in the antiviral area could be due to targeting drugs at "non-self" genomes and to the patient population that is tolerant of manageable side effects and adaptable to inconvenient dosing. Aimed at medicinal chemists and emerging drug discovery scientists, the book is organized according to the various strategies deployed for the discovery and optimization of initial lead compounds. This book focuses on capturing tactical aspects of problem solving in antiviral drug design, an approach that holds special appeal for those engaged in antiviral drug development, but also appeals to the broader medicinal chemistry community based on its focus on tactical aspects of drug design.
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.
A crucial issue for antiviral therapy is the fact that all antiviral substances rapidly select for resistance; thus, monitoring and overcoming resistance has become a most important clinical paradigm of antiviral therapy. This calls for cautious use of antiviral drugs and implementation of combination therapies. In parallel, efforts in drug discovery have to be continued to develop compounds with novel mode-of-action and activity against resistant strains. This book reviews the current status of antiviral therapy, from the roads to development of new compounds to their clinical use and cost effectiveness. Individual chapters address in more detail all available drug classes and outline new approaches currently under development.
This volume will be aimed at medicinal chemistry and emerging drug discovery scientists.
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.
By focusing on general molecular mechanisms of antiviral drugs rather than therapies for individual viruses, this ready reference provides the critical knowledge needed to develop entirely novel therapeutics and to target new viruses. It begins with a general discussion of antiviral strategies, followed by a broad survey of known viral targets, such as reverse transcriptases, proteases, neuraminidases, RNA polymerases, helicases and primases, as well as their known inhibitors. The final section contains several cases studies of recent successful antiviral drug development. Edited by Erik de Clercq, the world authority on small molecule antiviral drugs, who has developed more new antivirals than anyone else.
This book focuses on new small molecule approaches to combat viral infections. The chapters describe the discovery and development from bench through the clinic of relatively recently-approved antiviral drugs and compounds in advanced clinical development. Organized by a virus (such as HIV, HCV, RSV, influenza, HBV and CMV) and written by top academic and industrial authorities in the field, the book provides a unique opportunity to study, understand and apply discovery and development principles and learning without the need for an individual to research, analyze and synthesize all immense sourcing references. Topics showcase challenges and solutions of issues encountered, offering tremendous experience accumulated over many years of research that will be particularly useful to basic and bench scientists as well as clinicians as they continue discovering and developing new drugs and therapies.
Viral Pathogenesis: From Basics to Systems Biology, Third Edition, has been thoroughly updated to cover topical advances in the evolving field of viral pathogenesis, while also providing the requisite classic foundational information for which it is recognized. The book provides key coverage of the newfound ability to profile molecular events on a system-wide scale, which has led to a deeper understanding of virus-host interactions, host signaling and molecular-interaction networks, and the role of host genetics in determining disease outcome. In addition, the content has been augmented with short chapters on seminal breakthroughs and profiles of their progenitors, as well as short commentaries on important or controversial issues in the field. Thus, the reader will be given a view of virology research with perspectives on issues such as biomedical ethics, public health policy, and human health. In summary, the third edition will give the student a sense of the exciting new perspectives on viral pathogenesis that have been provided by recent developments in genomics, computation, modeling, and systems biology. - Covers all aspects of viral infection, including viral entry, replication, and release, as well as innate and adaptive immunity and viral pathogenesis - Provides a fresh perspective on the approaches used to understand how viruses cause disease - Features molecular profiling techniques, whole genome sequencing, and innovative computational methods - Highlights the use of contemporary approaches and the insights they provide to the field
Virus as Composition, Complexity, Quasispecies, Dynamics, and Biological Implications, Second Edition, explains the fundamental concepts surrounding viruses as complex populations during replication in infected hosts. Fundamental phenomena in virus behavior, such as adaptation to changing environments, capacity to produce disease, and the probability to be transmitted or respond to treatment all depend on virus population numbers. Concepts such as quasispecies dynamics, mutations rates, viral fitness, the effect of bottleneck events, population numbers in virus transmission and disease emergence, and new antiviral strategies are included. The book's main concepts are framed by recent observations on general virus diversity derived from metagenomic studies and current views on the origin and role of viruses in the evolution of the biosphere. - Features current views on key steps in the origin of life and origins of viruses - Includes examples relating ancestral features of viruses with their current adaptive capacity - Explains complex phenomena in an organized and coherent fashion that is easy to comprehend and enjoyable to read - Considers quasispecies as a framework to understand virus adaptability and disease processes
Drug repurposing or drug repositioning is a new approach to presenting new indications for common commercial and clinically approved existing drugs. For example, chloroquine, an old antimalarial drug, showed promising results for treating COVID-19, interfering with MDR in several types of cancer, and chemosensitizing human leukemic cells.This book focuses on the hypothesis, risk/benefits, and economic impacts of drug repurposing on drug discovery in dermatology, infectious diseases, neurological disorders, cancer, and orphan diseases. It brings together up-to-date research to provide readers with an informative, illustrative, and easy-to-read book useful for students, clinicians, and the pharmaceutical industry.