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 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 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 A Kinetic Analysis of Human Immunodeficiency Virus Reverse Transcriptase written by Shawn Patrick Zinnen and published by . This book was released on 1994 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Human Immunodeficiency Virus Type 1 Reverse Transcriptase written by Michael Hottiger and published by . This book was released on 1995 with total page 108 pages. Available in PDF, EPUB and Kindle. Book excerpt: Zsfassung in dt. Sprache.
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 Characterizing Human Immunodeficiency Virus Type 1 Reverse Transcriptase and Integrase Interaction written by Shewit Tekeste and published by . This book was released on 2014 with total page 83 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human immunodeficiency virus type 1 (HIV-1) replication requires the reverse transcription of its RNA genome into double-stranded DNA copies within the cytoplasm before integration into the host chromosome. Reverse transcriptase (RT) and integrase (IN) are the viral enzymes responsible for catalyzing the essential steps of reverse transcription and integration, respectively. While numerous studies have led to a greater understanding of the functional roles that RT and IN individually play in HIV-1 replication, little is known about the functional role of RT-IN complex formation in vivo. We hypothesize that RT-IN interaction has functional significance in HIV-1 reverse transcription and replication kinetics. We have mapped the putative binding domain of RT on IN to nine residues on the IN C-terminal domain (CTD). We tested the significance of RT-IN interaction on reverse transcription and viral replication, and identified the step at which viral replication of these IN mutants become defective. We observed impairment of viral cDNA synthesis in viruses harboring IN mutations at the putative RT-binding surface, supporting our hypothesis that the RT-IN interaction during the reverse transcription step is biologically relevant. We have developed a pharmacological approach to study and screen for inhibitors against the RT-IN interaction. Lastly, we have also initiated biochemical studies to determine the IN binding domain domain on RT to contribute to the full understanding of the binding mechanism.
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 Molecular Analysis of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase in Infectious Virus written by Alok Mohan Mulky and published by . This book was released on 2005 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Mechanism of the DNA Polymerase Activity of Human Immunodeficiency Virus Reverse Transcriptase written by Jen-Chih Hsieh and published by . This book was released on 1994 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Structure function Studies on the Human Immunodeficiency Virus Type 1 Reverse Transcriptase written by Michael Rostam Bavand and published by . This book was released on 1993 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Human Immunodeficiency Virus Type 1 Reverse Transcriptase written by Timothy S. Fisher and published by . This book was released on 2002 with total page 654 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Structural Dynamics of Human Immunodeficiency Virus Type I Reverse Transcriptase written by James Malcolm Seckler and published by . This book was released on 2011 with total page 168 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human Immunodeficiency Virus Type 1 Reverse Transcriptase (RT) is the protein in HIV responsible for transcribing viral RNA into double stranded DNA, making it an essential component in viral infectivity and the most popular target for anti-viral therapies for HIV. Over the years, a plethora of inhibitors for RT have been developed, and many of them are currently approved for clinical use. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) are small molecules that act as non-competitive, allosteric inhibitors of RT, binding in a binding pocket inside of the polymerase domain of RT and hampering enzymatic activity. Although this is a widely used class of viral inhibitor, the mechanism of inhibition is currently unknown. In addition to this, most current knowledge of RT is concentrated on the heterodimer, while little is known of the monomeric precursors to this structure. In this study we employ HXMS and SAXS to probe the solution structural dynamics and solution structure of RT heterodimer and monomers. We show that the p51 subunit does not form the stable core of the protein. Rather the core consists of the fingers and palm subdomains of both subunits. A ß-sheet that forms half of the NNRTI binding site undergoes slow cooperative unfolding, which is slowed by several orders of magnitude upon NNRTI binding. In addition to this, HXMS analysis reveals an allosteric network of regions that spans both subunits of the RT heterodimer. This network is thought to play a vital role in RT inhibition. The structural dynamics and solution structure of RT monomers were determined, revealing that the monomers were structured but more flexible in solution compared to the solution structure of the heterodimer. HXMS revealed that the monomers had nearly identical secondary structure, with the main difference being slow cooperative unfolding in the p66 thumb subdomain. SAXS revealed that both monomers exist in an ensemble of conformation. The polymerase domain of both monomers exists both in an open p66-like conformation, a closed p51-like conformation, and several unique conformations. This research lays the foundation for a novel method of drug screening and discovery.
Download or read book Mechanisms of Viral Recombination by Human Immunodeficiency Virus Type 1 Reverse Transcriptase written by Jin Kyung Kim and published by . This book was released on 1998 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 The Roles of Human Immunodeficiency Virus Reverse Transcriptase and Nucleocapsid Protein Inviral Recombination written by Lorna Rodríguez-Rodríguez and published by . This book was released on 1996 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt:
