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Evolution of Anti-HIV Drug Resistance

Author : Lutz Gürtler
Publisher : S. Karger AG (Switzerland)
Page : 0 pages
File Size : 31,23 MB
Release : 2012-01-24
Category :
ISBN : 9783805599023

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Despite recent advances in antiretroviral therapy treating HIV drug resistance remains a challenge. With the growing number of anti-HIV drugs and the enormous variant space accessible by viral evolution, manual selection of effective anti-HIV therapies has become complex. This publication represents a recent update on the determination of antiretroviral drug resistance determination, its computer program-assisted interpretation and beneficial effect on the treatment of HIV-1- and HIV-2-infected patients. Starting with the description of the human immunodeficiency viruses and their mutation frequency it goes on to discuss methods of resistance determination and bioinformatic-guided algorithm of interpretation, the fate of patients in large cohorts benefitting from improved therapeutic interventions and limitations in individual patients and HIV-2 infection. Furthermore Pyro 454 sequencing and interpretation of single amino acids in the context of all involved mutations in antiretroviral drug resistance are described and R5 and X4 differentiation by nucleic acid sequencing and susceptibility of HIV to a maraviroc treatment regimen are specified. This special issue of Intervirology will be of benefit to medical doctors involved in the treatment of HIV-infected patients as well as to pharmacologists, bioinformaticians and laboratory personnel working in the field of drug resistance analysis, drug design and antivirals. Furthermore it is a valuable resource for researchers involved in the confection of new drugs and interactions of old drugs as well as in assays of antiviral drug resistance.

Virus Dynamics : Mathematical Principles of Immunology and Virology

Author : Martin Nowak
Publisher : Oxford University Press, UK
Page : 253 pages
File Size : 39,15 MB
Release : 2000-11-23
Category :
ISBN : 0191588512

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This groundbreaking book describes the emerging field of theoretical immunology, in particular the use of mathematical models to describe the spread of infectious diseases within patients. It reveals fascinating insights into the dynamics of viral and other infections, and the interactions between infectious agents and immune responses. Structured around the examples of HIV/AIDS and hepatitis B, Nowak and May show how mathematical models can help researchers to understand the detailed dynamics of infection and the effects of antiviral therapy. Models are developed to describe the dynamics of drug resistance, immune responses, viral evolution and mutation, and to optimise the design of therapy and vaccines. - ;We know, down to the tiniest details, the molecular structure of the human immunodeficiency virus (HIV). Yet despite this tremendous accomplishment, and despite other remarkable advances in our understanding of individual viruses and cells of the immune system, we still have no agreed understanding of the ultimate course and variability of the pathogenesis of AIDS. Gaps in our understanding like these impede our efforts towards developing effective therapies and preventive vaccines. Martin Nowak and Robert M May describe the emerging field of theoretical immunology in this accessible and well- written text. Using mathematical modelling techniques, the authors set out their ideas about how populations of viruses and populations of immune system cells may interact in various circumstances, and how infectious diseases spread within patients. They explain how this approach to understanding infectious diseases can reveal insights into the dynamics of viral and other infections, and the interactions between infectious agents and immune responses. The book is structured around the examples of HIV/AIDS and Hepatitis B virus, although the approaches described will be more widely applicable. The authors use mathematical tools to uncover the detailed dynamics of the infection and the effects of antiviral therapy. Models are developed to describe the emergence of drug resistance, and the dynamics of immune responses, viral evolution, and mutation. The practical implications of this work for optimisation of the design of therapy and vaccines are discussed. The book concludes with a glance towards the future of this fascinating, and potentially highly useful, field of study. - ;... an excellent introduction to a field that has the potential to advance substantially our understanding of the complex interplay between virus and host - Nature

Handbook of Antimicrobial Resistance

Author : Matthias Gotte
Publisher : Springer
Page : 0 pages
File Size : 37,12 MB
Release : 2018-02-12
Category : Medical
ISBN : 9781493906932

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While many volumes have been written about various aspects of antimicrobial resistance, this book is a comprehensive reference work. All manifestations of resistance are addressed: viral; bacterial, parasitical and fungal are given dedicated sections. The underlining molecular mechanisms, which depend not only on the microbe but on the specific drug (target), are highly diverse. This work discusses and compares the biological, biochemical and structural aspects of resistance and its evolution.

Structural Biology in Drug Discovery

Author : Jean-Paul Renaud
Publisher : John Wiley & Sons
Page : 1367 pages
File Size : 16,27 MB
Release : 2020-01-09
Category : Medical
ISBN : 1118900502

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With the most comprehensive and up-to-date overview of structure-based drug discovery covering both experimental and computational approaches, Structural Biology in Drug Discovery: Methods, Techniques, and Practices describes principles, methods, applications, and emerging paradigms of structural biology as a tool for more efficient drug development. Coverage includes successful examples, academic and industry insights, novel concepts, and advances in a rapidly evolving field. The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a valuable reference and resource that: Presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology Includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design Emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures Illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins

HIV-1 Integrase

Author : Nouri Neamati
Publisher : John Wiley & Sons
Page : 710 pages
File Size : 30,57 MB
Release : 2011-08-10
Category : Science
ISBN : 1118015363

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This book comprehensively covers the mechanisms of action and inhibitor design for HIV-1 integrase. It serves as a resource for scientists facing challenging drug design issues and researchers in antiviral drug discovery. Despite numerous review articles and isolated book chapters dealing with HIV-1 integrase, there has not been a single source for those working to devise anti-AIDS drugs against this promising target. But this book fills that gap and offers a valuable introduction to the field for the interdisciplinary scientists who will need to work together to design drugs that target HIV-1 integrase.

Antiviral Drug Resistance

Author : Douglas D. Richman
Publisher : Wiley
Page : 324 pages
File Size : 10,15 MB
Release : 1996-12-02
Category : Medical
ISBN : 9780471961208

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The study of antiviral drug resistance has provided important insights into the structure of virus enzymes, the functions of certain genes, mechanisms of action of antiviral drugs, the design of new antiviral compounds and the pathogenesis of viral diseases. The emergence of resistant strains must be explored at all stages of drug development: during the preclinical evaluation of candidate compounds; during the early clinical evaluation of new drugs; and as part of epidemiological surveillance for the prevalence of resistance during use of approved treatments. Accumulating understanding of antiviral drug resistance thus reflects progress in the chemotherapy of viral infection. Antiviral Drug Resistance provides state-of-the-art coverage of the basic and clinical aspects of this subject. It deals with the basic science, including the mechanisms of drug resistance and drug action, genetics of drug resistance, cross resistance, and X-ray crystallographic structural aspects of resistance, as well as the clinical aspects, including issues of assay of susceptibility of clinical isolates, descriptive aspects of emergence of reduced susceptibility, and clinical significance and impact of resistance. As such this unique volume will be essential to basic researchers in drug discovery and viral pathogenesis, as well as clinicians involved in antiviral chemotherapy.

Introduction to Biological and Small Molecule Drug Research and Development

Author : Arun K. Ghosh
Publisher : Elsevier Inc. Chapters
Page : 43 pages
File Size : 29,38 MB
Release : 2013-05-07
Category : Science
ISBN : 0128062037

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The development of HIV protease inhibitors (PIs) and their inclusion in highly active antiretroviral therapies (HAARTs) marked the beginning of a treatment breakthrough in the management of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). The HAART treatment regimen can cut HIV viral load to undetectable levels. Nonetheless, the rapid emergence of HIV drug resistance has continued to seriously compromise long-term treatment options for HIV-infected patients. Our structure-based design strategy to develop PIs that specifically target the enzyme's backbone atoms has resulted in a number of very potent inhibitors with superior drug resistance profiles. Of particular note, our development of stereochemically defined bis(tetrahydrofuranyl) urethane as a high-affinity P2 ligand has led to the development of exceedingly potent inhibitors. One of these inhibitors, darunavir, has shown exceptional potency against the HIV-1 virus and superior activity against multi-PI-resistant viral strains. Our backbone binding strategy was corroborated with detailed crystal structure analyses of darunavir-bound protease complexes which revealed a series of conserved interactions between the inhibitor and key backbone atoms of HIV-1 protease. Darunavir first received accelerated US Food and Drug Administration approval in 2006 for highly treatment-experienced patients with little therapeutic options. It has now become a leading PI in the fight against HIV infection and drug resistance.

Disease Control Priorities, Third Edition (Volume 6)

Author : King K. Holmes
Publisher : World Bank Publications
Page : 1027 pages
File Size : 25,3 MB
Release : 2017-11-06
Category : Medical
ISBN : 1464805253

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Infectious diseases are the leading cause of death globally, particularly among children and young adults. The spread of new pathogens and the threat of antimicrobial resistance pose particular challenges in combating these diseases. Major Infectious Diseases identifies feasible, cost-effective packages of interventions and strategies across delivery platforms to prevent and treat HIV/AIDS, other sexually transmitted infections, tuberculosis, malaria, adult febrile illness, viral hepatitis, and neglected tropical diseases. The volume emphasizes the need to effectively address emerging antimicrobial resistance, strengthen health systems, and increase access to care. The attainable goals are to reduce incidence, develop innovative approaches, and optimize existing tools in resource-constrained settings.

Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection

Author : World Health Organization
Publisher :
Page : 429 pages
File Size : 50,70 MB
Release : 2016
Category : AIDS (Disease)
ISBN : 9789241549684

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These guidelines provide guidance on the diagnosis of human immunodeficiency virus (HIV) infection, the use of antiretroviral (ARV) drugs for treating and preventing HIV infection and the care of people living with HIV. They are structured along the continuum of HIV testing, prevention, treatment and care. This edition updates the 2013 consolidated guidelines on the use of antiretroviral drugs following an extensive review of evidence and consultations in mid-2015, shared at the end of 2015, and now published in full in 2016. It is being published in a changing global context for HIV and for health more broadly.

The Evolution of HIV

Author : Keith A. Crandall
Publisher : JHU Press
Page : 524 pages
File Size : 20,55 MB
Release : 1999-04-26
Category : Medical
ISBN : 9780801861512

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Wolinsky.-- "European Molecular Biology Organization Reports"