Download or read book Human Immunodeficiency Virus Reverse Transcriptase written by Stuart LeGrice and published by Springer Science & Business Media. This book was released on 2013-07-23 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Reverse Transcriptase (RT) of Human Immunodeficiency Virus Type 1 (HIV-1) arguably ranks amongst one of the most extensively studied retroviral enzymes. Heterologous expression and purification of HIV-1 RT in the early eighties, approval of the first nucleoside analogue RT inhibitor (NRTI) in 1987, discovery of resistance to RT inhibitors, approval of the first non-nucleoside analogue RT inhibitor (NNRTI) in 1996 and the various crystal structures of RT with and without bound substrate(s) and/or inhibitors represent only a few of the important milestones that describe the a bench-to-bedside success in the continuing effort to combat HIV-1 infection and its consequences. Nucleoside and nonnucleoside RT inhibitors remain important components in frequently used drug regimens to treat the infection. RT inhibitors also play important roles in recently validated strategies to prevent transmission of the virus. The relevance of HIV-1 RT as a drug target has simultaneously triggered interest in basic research studies aimed at providing a more detailed understanding of interactions between proteins, nucleic acids, and small molecule ligands in general terms. In light of the ever-growing knowledge on structure and function of HIV-1 RT, this enzyme serves as a valuable “model system” in efforts to develop novel experimental tools and to explain biochemical processes. This monograph is designed to provide an overview of important aspects in past and current HIV-1 RT research, with focus on mechanistic aspects and translation of knowledge into drug discovery and development. The first section includes chapters with emphasis placed on the coordination of the RT-associated DNA polymerase and ribonuclease H (RNase H) activities. The second covers mechanisms of action and future perspectives associated with NRTIs and NNRTIs, while the third section includes chapters focusing on novel strategies to target the RT enzyme. Chapters of the final part are intended to discuss mechanisms involved in HIV variability and the development of drug resistance. We hope that these contributions will stimulate interest, and encourage research aimed at the development of novel RT inhibitors. The lack of bona fide RNase H inhibitors with potent antiviral activity provides an example for challenges and opportunities in the field.
Download or read book Active Site Studies of Human Immunodeficiency Virus Reverse Transcriptase written by Laura Louise Watts Mitchell and published by . This book was released on 1991 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book HIV 1 Integrase written by Nouri Neamati and published by John Wiley & Sons. This book was released on 2011-08-10 with total page 710 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Biochemical Characteristics of Different Subtypes of Human Immunodeficiency Virus Type 1 Reverse Transcriptase and Its Interactions with the Host Factor written by Seongmi Kim and published by . This book was released on 2017 with total page 87 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human immunodeficiency virus (HIV) is divided into type 1 (HIV-1) and type 2 (HIV-2). Whereas HIV-2 accounts for 5% of global infections, HIV-1 is responsible for 95% of the global pandemic. HIV-1 is classified into four groups; M, N, O and P. Group M is the most prevalent, including subtypes or clades of A-D, F-H, J, K, over 100 Circulating Recombinant Forms (CRFs), and several Unique Recombinant Forms (URFs). In developed countries (i.e. countries in North America, Western Europe, and Australia), HIV-1B is the most prevalent strain. However, it accounts for only about 12% of worldwide infections. On the other hand, HIV-1C, which is most prevalent in Low- and Middle-Income Countries (LMICs) (e.g. India, Brazil, and many countries in Sub-Saharan Africa), accounts for [approximately]52% of all HIV infections. Due to its prevalence in developed countries, HIV-1B has been the major target of HIV studies and anti-HIV drug development. However, it has been reported that HIV-1non-B patients have higher rates of treatment failure than HIV-1B patients. To understand the mechanism behind this observation, we applied in vitro biochemical assays, which were performed with four patient-derived reverse transcriptase (RT) proteins isolated from HIV-1B, HIV-1C, CRF01_AE, and CRF02_AG viruses. RT is the HIV enzyme that generates viral DNA from genomic RNA during the early stages of infection, and it is the target for many anti-HIV drugs. RT inhibitors are divided into two types depending on their structure. First, Nucleoside/nucleotide Reverse Transcriptase Inhibitors (NRTIs), which bind the active site of the RT and act as chain terminators. In addition, a new type of NRTI, called 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), works as a translocation inhibitor. Second, Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) inhibit RT by binding to an allosteric site. Nevirapine (NVP) belongs to the first generation of NNRTIs, however HIV-1 develops resistance mutations frequently during NVP treatment. Rilpivirine (RPV) has been developed to target NVP-resistant viruses but it is not frequently used in LMICs. In this study, we determined the biochemical characteristics of HIV-1 RTs from various subtypes and determined kinetic constants of inhibition by EFdA, NVP, and RPV. The results show that all of the tested HIV-1 RTs incorporate EFdA with better efficiency than their natural cognate substrate, dATP, which suggests that EFdA would be effective against all of the tested HIV-1 subtypes. Furthermore, generally NVP binds RTs with a lower affinity than RPV, implying that NVP would be a less effective inhibitor than RPV. However, in the case of CRF02_AG RT, NVP binds with similar affinity to RPV, suggesting CRF02_AG patients may respond better to NVP than patients infected with other subtypes. HIV-1C has less binding affinity to RPV than other subtypes, which is consistent with clinical reports showing that HIV-1C patients have a higher rate of treatment failure with RPV. Finally, we have studied the effect of a host factor, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G (APOBEC3G), on HIV-1 RT. APOBEC3G (A3G) has been reported to inhibit several retroviral infections. To date, there are two established mechanisms of this inhibition, which are hyper-mutagenesis and roadblock. In this study, we investigated a third mechanism, the direct inhibition of HIV-1 RT, using in vitro RT assays. Our results showed that A3G does inhibit the activity of HIV-1 RT by affecting the catalytic rate of dNTP incorporation (k[subscript cat]), supporting the direct inhibition mechanism. Interestingly, A3G had similar inhibitory activity against a related viral RT (from Moloney Murine Leukemia Virus), but no activity against DNA polymerase I.
Download or read book Encyclopedia of AIDS written by Thomas J. Hope and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Nucleic Acid Polymerases written by Katsuhiko S. Murakami and published by Springer Science & Business Media. This book was released on 2013-10-22 with total page 342 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book New Strategies for the Development of Polymerase Active Site Inhibitors of HIV 1 Reverse Transcriptase written by Jean Bernatchez and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "The reverse transcriptase (RT) of the human immunodeficiency virus-1 (HIV-1) displays both DNA- and RNA-dependent polymerase and RNase H activities. The enzyme remains an important target in the design of antiretroviral small molecules; however, the emergence of viral clones resistant to currently approved RT inhibitors complicates the treatment management of the disease, and has driven the search for new small molecules which are not affected by classical resistance pathways. In this work, three separate structural types of investigational inhibitors of RT polymerase activity, each with distinct mechanisms of action, are presented. These include derivatives of mesoxalic acid, the CORK series of compounds, and ganciclovir-triphosphate. Derivatives of mesoxalic acid trap the pre-translocated complex of RT, and have different binding determinants and resistance profiles from the prototypical inhibitor of this class, phosphonoformic acid (PFA).The second group of small molecules discussed herein are nucleotide competing reverse transcriptase inhibitors (NcRTIs), which trap the post-translocated complex of RT and which compete with the natural nucleotide for binding to the enzyme. The CORK series, a structurally-distinct type of NcRTIs, are shown to not be incorporated by the enzyme and to trap the post-translocated state of RT; profiling of the most potent CORK compound, CORK 27, reveals its susceptibility to the multidrug resistance Q151M cluster.The final section discusses how the non-obligate chain terminator ganciclovir-triphosphate (GCV-TP), used in human cyclomegalovirus (HCMV) treatment, acts as a delayed-chain terminator of DNA synthesis by HIV-1 RT. The determinants for GCV-TP inhibition across four different viral polymerase are analyzed for comparative purposes.These studies present three new paths for RT inhibition that are distinct from classical RT inhibitors, and as such represent significant leads for the development of novel treatments against HIV-1." --
Download or read book Handbook of Antimicrobial Resistance written by Matthias Gotte and published by Springer. This book was released on 2018-02-12 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Structural Analysis of the Catalytic Region of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase written by Jason Derek Merker and published by . This book was released on 1996 with total page 62 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Advances in Metallodrugs written by Shahid Ul-Islam and published by John Wiley & Sons. This book was released on 2020-07-08 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is organized into 12 important chapters that focus on the progress made by metal-based drugs as anticancer, antibacterial, antiviral, anti-inflammatory, and anti-neurodegenerative agents, as well as highlights the application areas of newly discovered metallodrugs. It can prove beneficial for researchers, investigators and scientists whose work involves inorganic and coordination chemistry, medical science, pharmacy, biotechnology and biomedical engineering.
Download or read book Reverse Transcriptase Inhibitors in HIV AIDS Therapy written by Gail Skowron and published by Springer Science & Business Media. This book was released on 2007-11-10 with total page 536 pages. Available in PDF, EPUB and Kindle. Book excerpt: A magisterial survey of all aspects of the reverse transcriptase inhibitors (RTIs) used to treat HIV/AIDS, including drug discovery, pharmacology, development of drug resistance, toxicity, and prevention of mother-to-child transmission of HIV/AIDS. The authors synthesize our current understanding of the role of reverse transcriptase in the viral life cycle, describe the discovery and development of eight nucleoside and nucleotide analogs that represent milestones in treatment history, and thoroughly discuss the question of toxicity and resistance to this class of drugs. They also address three non-nucleoside RTIs and their pharmacokinetics and comparative clinical efficacy, new RTIs currently under development, and the impact of approved agents on treatment, in general, and on vertical transmission in the developing world.
Download or read book Human Retroviruses written by Bryan Cullen and published by Oxford University Press. This book was released on 1993 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first book to specifically cover the molecular biology of retroviruses - of immense importance since the high profile of HIV. International contributors provide detailed reviews of the latest knowledge. An excellent text for both medical and non-medical researchers, it also serves as an illuminating introduction for scientists active in other areas.
Download or read book Nano inspired Biosensors for Protein Assay with Clinical Applications written by Genxi Li and published by Elsevier. This book was released on 2018-08-29 with total page 378 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nano-inspired Biosensors for Protein Assay with Clinical Applications introduces the latest developments in nano-inspired biosensing, helping readers understand both the fundamentals and frontiers in this rapidly advancing field. In recent decades, there has been increased interest in nano-inspired biosensors for clinical application. Proteins, e.g. antigen-antibody, tumor markers and enzymes are the most important target in disease diagnosis, and a variety of biosensing techniques and strategies have been developed for protein assay. This book brings together all the current literature on the most recent advances of protein analysis and new methodologies in designing new kinds of biosensors for clinical diagnostic use. Provides a single source of information on the latest developments in the field of biosensors for protein analysis and clinical diagnosis Focuses on biosensors fabricated with nanomaterials and nanotechnology Gives detailed methodologies for designing and fabricating nano-inspired biosensors
Download or read book The Human Immunodeficiency Virus written by Emilio Emini and published by Princeton University Press. This book was released on 2021-04-13 with total page 546 pages. Available in PDF, EPUB and Kindle. Book excerpt: The past few years have witnessed an explosive increase in our collective knowledge of the biology of the human immunodeficiency virus (HIV). Researchers have acquired new understanding of the virus's biochemistry, molecular biology, pathogenesis, genetics, and immunobiology. Resulting therapeutic advances have significantly prolonged the lives of thousands. Yet, the need to develop better therapies is ever more acute and--given the virus's continued spread through the human population--the need for an effective vaccine is urgent. These goals can be accomplished only through the experienced synthesis of information from the many disciplines participating in HIV research and through the insights of new investigators. This volume is designed to lower the barriers imposed on investigators by the sheer volume of available information--information that often can be found only in far-flung and specialized journals. It provides, in a single resource, an in-depth overview of the diverse areas that constitute HIV research. The result is a broad introduction for students and researchers new to the field as well as an integrated overview for researchers specialized in particular areas of HIV investigation. The volume will also benefit those seeking technical understanding of the virus's biology, including physicians treating HIV-infected patients. Each chapter is a comprehensive presentation of one area of current AIDS research--including work on the virus life cycle, epidemiology, genetics, protease and reverse transcriptase inhibitors, receptor and co-receptor interactions, therapeutic targets, clinical treatment, immunobiology, and vaccines--written by a leading researcher in that area. The contributors are Jon P. Anderson, Jan Balzarini, Elana Cherry, Thomas J. Coates, Chris Collins, Jon H. Condra, Mark B. Feinberg, Richard B. Gaynor, Matthias Götte, Daria J. Hazuda, Spyros Kalams, Nathaniel R. Landau, Gerald H. Learn, Norman L. Letvin, James I. Mullins, Willscott E. Naugler, David Nickle, Matthew Rain, Allen G. Rodrigo, Daniel Shriner, Shalom Spira, Mario Stevenson, Todd Summers, Catherine Ulich, Joseph P. Vacca, Mark A. Wainberg, Bruce D. Walker, and Yang Wang.
Download or read book Diagnostics to Pathogenomics of Sexually Transmitted Infections written by Sunit Kumar Singh and published by John Wiley & Sons. This book was released on 2018-12-06 with total page 442 pages. Available in PDF, EPUB and Kindle. Book excerpt: Comprehensively explores sexually transmitted diseases, from epidemiology, causative pathogens, clinical impact, and immunology, to management strategies utilizing new strategies of genomics and next-generation diagnostic tools Sexually transmitted infections (STI) are very common worldwide. More than 20 different STIs have been identified, and about 19 million men and women are infected each year in the United States alone. This book looks at the complete picture of common STIs— how they form, evolve, and transmit, as well as how they can be treated and managed with modern techniques, medicines, and tools. Diagnostics to Pathogenomics of Sexually Transmitted Infections runs the spectrum of discussion ranging from introduction of causative pathogen, their pathogenesis to epidemiology, immunology, to anatomy and physiology of human genitalia and management strategies. The book offers in-depth chapter coverage on effect of probiotics on reproductive health; mucosal immunity in sexually transmitted infections; the role of circumcision in preventing STIs; Human Immunodeficiency Virus (HIV); genital herpes; molluscum contagiosum; genital warts; chlaymydia trachomatis; donovanosis; gonorrhoea; treponematoses; genital mycoplasms; bacterial vaginosis; vulvovaginal candidiasis; chlaymydia; scabies; chancroid, yeast infections; and more. Comprehensively compiles most of the major sexually transmitted infections Presents updated information on clinical aspects of sexually transmitted infections Examines the priorities in pathogenesis of human sexually transmitted infections and discusses new strategies of genomics and next-generation diagnostic tools used for detection of such pathogens Explores the future of rapid molecular diagnostic techniques and the challenges posed in the diagnosis of human STIs Includes bench to bedside content that will appeal to both basic and clinical researchers By offering the latest knowledge about recent advances in sexually transmitted infections in an interdisciplinary fashion, Diagnostics to Pathogenomics of Sexually Transmitted Infections is the perfect book for virologists, microbiologists, infectious disease experts, vaccinologists, biomedical researchers, clinicians, pharmacologists, and public health specialists.
Download or read book HIV and Disability written by Institute of Medicine and published by National Academies Press. This book was released on 2010-11-17 with total page 217 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Social Security Administration (SSA) uses a screening tool called the Listing of Impairments to identify claimants who are so severely impaired that they cannot work at all and thus qualify for disability benefits. In this report, the Institute of Medicine (IOM) makes several recommendations for improving SSA's capacity for determining disability benefits more accurately and quickly using the HIV Infection Listings.
Download or read book Proteases as Targets for Therapy written by Klaus, von der Helm and published by Springer. This book was released on 2012-10-10 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: With contributions by numerous experts
