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Characterization Of The Hepatitis C Virus Ns5b Rna Dependent Rna Polymerase
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Book Synopsis Characterization of the Hepatitis C Virus NS5b RNA-Dependent RNA Polymerase by : Megan Heather Powdrill
Download or read book Characterization of the Hepatitis C Virus NS5b RNA-Dependent RNA Polymerase written by Megan Heather Powdrill and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Kinetic Characterization of the Inhibition, Excision Mechanisms, and Fidelity of Hepatitis C Virus RNA-dependent RNA Polymerase by : Brian Villalba
Download or read book Kinetic Characterization of the Inhibition, Excision Mechanisms, and Fidelity of Hepatitis C Virus RNA-dependent RNA Polymerase written by Brian Villalba and published by . This book was released on 2020 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt: NS5B is the RNA-dependent RNA polymerase that catalyzes the replication of the Hepatitis C Virus genome. It is a major target for antiviral drugs including nucleoside analogs, such as the prodrugs Mericitabine and Sofosbuvir, which get metabolized to the chain terminators 2’-fluoro-2’-C-methylcytidine-5’-triphosphate and 2’fluoro-2’-C-methyluridine-5’-triphosphate, respectively. These analogs act as chain terminators after they are incorporated during RNA synthesis. Recently, work in our lab has shown that NS5B can efficiently remove chain-terminators by a nucleotide-mediated excision reaction that rescues RNA synthesis. In this study I use transient-state kinetics to probe the mechanism of inhibition for nucleoside analogs by directly measuring the rates of incorporation, pyrophosphorolysis, and ATP-mediated excision. I find that while CTP and CTP analogs are readily incorporated, they are efficiently excised. However, UTP is highly resistant to excision, and the 2’-C modifications of UTP serve to further inhibit excision. Furthermore, I use these same techniques to measure the in vitro fidelity of NS5B and uncover mechanisms for maintaining fidelity. The data demonstrate that NS5B exhibits a range of fidelity dependent on the nature of the mismatch. I also identified a slow-pyrophosphorolysis mechanism by NS5B used to further increase fidelity by decreasing k [subscript cat] /K [subscript m]. Together, this work offers insight into how current antiviral therapeutics escape excision, and can aid in the development of new antivirals by furthering our understanding of NS5B
Book Synopsis In Vitro Studies of the Hepatitis C Virus (HCV) RNA Dependent RNA Polymerase NS5B by : Elizabeth Margarita Quezada
Download or read book In Vitro Studies of the Hepatitis C Virus (HCV) RNA Dependent RNA Polymerase NS5B written by Elizabeth Margarita Quezada and published by . This book was released on 2008 with total page 440 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Investigation of the Hepatitis C Virus RNA Polymerase NS5B in Solution by Nuclear Magnetic Resonance and Its Interaction with Intrinsically Disordered Domain 2 of the NS5A Protein by : Luíza Mamigonian Bessa
Download or read book Investigation of the Hepatitis C Virus RNA Polymerase NS5B in Solution by Nuclear Magnetic Resonance and Its Interaction with Intrinsically Disordered Domain 2 of the NS5A Protein written by Luíza Mamigonian Bessa and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: NS5B is the hepatitis C virus (HCV) RNA-dependent RNA polymerase. This protein has been extensively studied by X-ray crystallography and shows an organization in three subdomains called fingers, palm and thumb. Whereas static crystallographic data are abundant, structural studies of this protein in solution are limited. Nuclear magnetic resonance (NMR) spectroscopy was used to study the 65 kDa NS5B in solution as well as its interaction with binding partners. It was characterized using selective isotopic labeling of isoleucine side-chain methyl groups, which gives rise to a simplified NMR spectrum with an improved signal-to-noise ratio. This characterization confirmed the presence of particular dynamics in the subdomains, especially in the thumb, as well as long-range effects that are transmitted through to other subdomains. Furthermore, this system was used to investigate the binding of the domain 2 of NS5A (NS5A-D2), a disordered domain of another HCV protein that has been shown to directly interact with NS5B in vitro. With paramagnetic relaxation enhancement experiments we showed that NS5A-D2 binds to NS5B via, at least, two binding sites on the thumb subdomain. As one of these sites was the binding site of allosteric inhibitor filibuvir, we characterized the binding of this small molecule to NS5B by NMR and found long-range effects of its binding throughout the polymerase. Finally, we studied the binding of a small RNA template strand to NS5B and found that both NS5A-D2 and filibuvir reduce but do not abolish the interaction between the polymerase and RNA. In sum, NMR spectroscopy was used to study dynamic properties of NS5B and its interactions with binding partners.
Book Synopsis Study of RNA Synthesis of Hepatitis C Virus in Vitro and in Cells of Hepatocarcinoma by : Neveen Ahmed El Sayed
Download or read book Study of RNA Synthesis of Hepatitis C Virus in Vitro and in Cells of Hepatocarcinoma written by Neveen Ahmed El Sayed and published by . This book was released on 2011 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The hepatitis C virus (HCV) NS5B protein displays a RNA-dependent RNA polymerase activity essential for replication of the viral RNA genome. This replication involves the synthesis of a replication intermediate of negative polarity. In vitro and likely in vivo, the NS5B initiates RNA synthesis by a de novo mechanism which requires specific interactions between the polymerase and viral RNA elements. In the first part of results, we described a combined structural and functional analysis of HCV-NS5B to study the role of a C-terminal segment (termed linker) and of GTP in RNA synthesis. Our results demonstrated that high GTP concentrations are necessary for the transition from the initiation to the elongation of RNA synthesis, and that linker mutations at position S556 did not modify the GTP requirement of NS5B for this transition. However, the initiation of RNA synthesis was greatly enhanced by a S556K mutation. These results together with a structural analysis point to the direct involvement of the linker in the de novo initiation of RNA synthesis. In the second and third parts of results, we studied the role of RNA elements in RNA synthesis. We demonstrated that the SL-E1 stem-loop formed by nucleotides 177-222 from the 3'-end of the HCV (-) RNA is important for RNA synthesis both in vitro by the recombinant NS5B and in Huh7 cells by HCV replication complex (RC). We also showed that SL-E1 is involved in initiation of RNA synthesis, at least in vitro. Then we studied the role of other viral RNA elements in core coding sequences (SLV and SLVI stem loops) and the involvement of the microRNA miR122 in RNA translation and RNA synthesis. For SLV and SLVI, our data did not show any clear role of these core-coding sequences or of their complement in the (-) RNA in RNA synthesis both in vitro by the recombinant NS5B and in cell culture by HCV-RC. We confirmed their negative effect on HCV-IRES translation through long range RNA-RNA interaction between SL-VI sequences and the 5'UTR and demonstrated that miR122 cannot disrupted this interaction and switches the region to an open conformation. Conversely, our data indicated that the SL-VI domain can counteract the negative effect of the interaction between the domain III of IRES and the 5BSL3.2 stem loop localized at the 3'end of the genome. These results point to the complexity of RNA/RNA and RNA/proteins interactions in the HCV replication cycle.
Book Synopsis Structural Dynamics and Inhibition of Hepatitis C RNA-dependent RNA Polymerase by : Jiawen Li
Download or read book Structural Dynamics and Inhibition of Hepatitis C RNA-dependent RNA Polymerase written by Jiawen Li and published by . This book was released on 2017 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: Combination therapy with direct-acting antivirals including nucleotide analogs (NAs) and non-nucleoside inhibitors (NNIs) targeting the RNA-dependent RNA polymerase NS5B have seen recent advancements and have dramatically improved the potency of Hepatitis C Virus (HCV) treatment. However, other than the identification of their site of action, very little is known about the inhibition mechanisms of these clinically relevant drugs. Lately, our lab has developed robust kinetic assays to characterize de novo RNA synthesis catalyzed by HCV NS5B, and then applied the assays to examine the mechanistic basis of action and to establish kinetic parameters governing the efficacy of various clinically relevant NAs and NNIs provided by three pharmaceutical companies (Gilead Sciences, Inc., Alios Biopharma and AbbVie Inc.). In addition, to probe the enzyme conformational dynamics of NS5B from de no initiation to elongation in the presence and absence of allosteric inhibitors, we collaborated with Dr. Patrick Wintrode on Hydrogen Deuterium exchange kinetics and Dr. Serdal Kirmizialtin on Molecular Dynamics simulations. Together, our collaborative efforts have provided a fundamental understanding of RNA-dependent RNA replication catalyzed by the HCV viral polymerase NS5B, and have established the inhibition mechanisms of anti-HCV agents. This work offers significant insights to aid the development of more effective drugs against HCV.
Book Synopsis De Novo Initiated RNA Synthesis by the Hepatitis C Virus RNA-dependent RNA Polymerase by : Sreedhar Reddy Chinnaswamy
Download or read book De Novo Initiated RNA Synthesis by the Hepatitis C Virus RNA-dependent RNA Polymerase written by Sreedhar Reddy Chinnaswamy and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Hepatitis C Virus (HCV) is a positive-strand RNA virus that has infected more than 3% of the world population. Chronic infections by the virus lead to cirrhosis and hepatocellular carcinoma. HCV is currently the leading cause for liver transplantation in the US. The nonstructural protein NS5B of HCV is the RNA-dependent RNA polymerase (RdRp) that replicates the viral RNA on host derived membranous structures. Structurally NS5B has the characteristic fingers, thumb and palm domains seen in all polymerase proteins. However, extensive interactions between the fingers and thumb domains completely encircle the active site of NS5B as seen in solved X-ray diffraction crystal structures. These interactions are primarily mediated by a short (35 residues) flexible loop called the Delta 1 loop. NS5B produced from heterologous systems can initiate RNA synthesis by a de novo initiation mechanism from 3'ends of RNA templates or can also extend from 3'ends of primers that are annealed stably to a template RNA in biochemical assays. The closed conformation of NS5B as per X-ray crystal structures can only accommodate a ssRNA but not a dsRNA, hence necessitating a conformational change between de novo initiation and elongation. The details of these conformational changes are not known and will prove to be important to design potent polymerase inhibitors. The study performed for this dissertation focused on the conformational requirements of NS5B during de novo initiation and primer extension (or elongation). Biochemical assays utilizing template RNAs that can lead to both de novo initiation and primer extension products were utilized, and a systematic mutational analysis of the template channel of the RdRp was performed. Mutants W397A and H428A were identified that showed only primer extension but no de novo initiation. Structural analysis of NS5B suggested that these residues were important contact points in the Delta 1 loop and thumb domain interactions. A deletion mutant, m26-30 with a five amino acid deletion at the apex of the Delta 1 loop also failed in de novo initiation but not primer extension reactions. Biophysical and gel shift assays showed that m26-30 was in a more open conformation than the WT enzyme. Furthermore, oligomerization of NS5B was demonstrated and its role in RNA synthesis was examined. It was found that the de novo initiation competent conformation of NS5B is maintained by oligomeric contacts between individual subunits, likely by stabilizing the Delta 1 loop and thumb domain interactions. Mutations disrupting the Delta 1 loop and thumb domain interactions as well as those in the allosteric GTP binding site induced conformational changes in the protein partially explaining the defect in de novo initiation activity in enzymes carrying those mutations. These results not only contribute to the overall mechanism of RNA synthesis in viral RdRps but also open new avenues for developing HCV polymerase inhibitors.
Book Synopsis Identification and Characterization of an RNA-dependent RNA Polymeras Encoded by the Hepatitis C Virus Non-structural 5B Region by : Reinoldus (Ronald) H. Al
Download or read book Identification and Characterization of an RNA-dependent RNA Polymeras Encoded by the Hepatitis C Virus Non-structural 5B Region written by Reinoldus (Ronald) H. Al and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author :Katsuhiko S. Murakami Publisher :Springer Science & Business Media ISBN 13 :3642397964 Total Pages :342 pages Book Rating :4.6/5 (423 download)
Book Synopsis Nucleic Acid Polymerases by : Katsuhiko S. Murakami
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.
Book Synopsis Structure and Functional Studies of the Hepatitis C Virus NS5B Gene Product - the RNA Dependent RNA Polymerase by : Damien O'Farrell
Download or read book Structure and Functional Studies of the Hepatitis C Virus NS5B Gene Product - the RNA Dependent RNA Polymerase written by Damien O'Farrell and published by . This book was released on 2002 with total page 570 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Viral Polymerases by : Satya Prakash Gupta
Download or read book Viral Polymerases written by Satya Prakash Gupta and published by Academic Press. This book was released on 2018-10-29 with total page 498 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral Polymerases: Structures, Functions and Roles as Antiviral Drug Targets presents in-depth study information on the structure and functions of polymerases and their roles in the lifecycle of viruses, and as drug targets. Viral polymerases constitute a vital component in the lifecycle of many viruses, such as human immunodeficiency virus (HIV), hepatitis viruses, influenza virus, and several others. They are essentially required for the replication of viruses. Thus, the polymerases that can be found in viruses (called viral polymerases) represent favorable targets for the design and development of antiviral drugs. Provides comprehensive, state-of-the-art coverage on virus infections, the virus lifecycle, and mechanisms of polymerase inhibition Analyzes the structure-activity relationships of inhibitors of each viral polymerase Presents a consistent and comprehensive coverage of all aspects of viral polymerases, including structure, function and their role as antiviral drug targets
Book Synopsis Advances in RNA Research and Application: 2011 Edition by :
Download or read book Advances in RNA Research and Application: 2011 Edition written by and published by ScholarlyEditions. This book was released on 2012-01-09 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in RNA Research and Application / 2011 Edition is a ScholarlyBrief™ that delivers timely, authoritative, comprehensive, and specialized information about RNA in a concise format. The editors have built Advances in RNA Research and Application: 2011 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about RNA in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Advances in RNA Research and Application: 2011 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Download or read book The Liver written by Irwin M. Arias and published by John Wiley & Sons. This book was released on 2020-03-09 with total page 1156 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.
Book Synopsis Facilitating SARS-CoV-2 RNA-Dependent RNA Polymerase (RdRp) Drug Discovery by the Aid of HCV NS5B Palm Domain Binders by : laila khaled
Download or read book Facilitating SARS-CoV-2 RNA-Dependent RNA Polymerase (RdRp) Drug Discovery by the Aid of HCV NS5B Palm Domain Binders written by laila khaled and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Corona Virus 2019 Disease (COVID-19) is a rapidly emerging pandemic caused by a newly discovered beta coronavirus, called Sever Acute Respiratory Syndrome Coronavirus 2 (SARS COV-2). SARS COV-2 is an enveloped, single stranded RNA virus that depends on RNA dependent RNA polymerase (RdRp) to replicate. Therefore, SARS COV-2 RdRp is considered as a promising target to cease virus replication. SARS COV-2 polymerase shows high structural similarity to Hepatitis C Virus-1b genotype (HCV-1b) polymerase. In our present study, we are relying on in-silico analysis to propose possible SARS COV-2 RdRp palm subdomain inhibitors to be used as a remedy for COVID-19. Additionally, providing an example of how to make use of a high quality custom-made DEKOIS 2.0 benchmark set as a procedure to elevate the virtual screening success rate against a vital target of the rapidly emerging pandemic. Arising from the high similarity between SARS COV-2 RdRp and HCV-1b polymerase, we used the reported small-molecule palm binders to HCV-1b polymerase to generate a high-quality DEKOIS 2.0 benchmark set and conducted a benchmarking against HCV-1b polymerase. The three highly cited and publicly available docking tools AutoDock Vina, FRED and PLANTS were benchmarked. Based on the benchmarking analysis, we used the highest performing docking tool to virtually screen FDA-approved drugs (from the DrugBank database) and the BindingDB database against the palm site of SARS COV-2 polymerase. From the benchmarking results, PLANTS showed the best performance with pROC-AUC value equals 0.97. Moreover, AutoDock Vina exhibited better-than-random performance with pROC-AUC value of 0.66 (above 0.43). Based on the virtual screening outcome, Quinupristin, which is an anti-biotic used in several bacterial infections, showed the best docking score among the screened compounds. In conclusion, Quinupristin as well as the top docking scored compounds are recommended to be biologically investigated as COVID-19 medications.
Book Synopsis Protein-protein Interactions of the Unstructured Domain II of Hepatitis C Virus NS5A by : Marianne Ngure
Download or read book Protein-protein Interactions of the Unstructured Domain II of Hepatitis C Virus NS5A written by Marianne Ngure and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "The hepatitis C virus (HCV) non-structural 5A (NS5A) protein is a multi-functional, RNA binding protein and an essential component of the HCV replication complex. It is subdivided into 3 domains; a highly structured domain I (DI), while DII and DIII are intrinsically unstructured yet mediate crucial interactions with several viral and cellular host factors. NS5A-DII protein mediates the interaction with Cyclophilin A (CypA), a cellular cis/trans isomerase essential for viral replication. Cyclosporine A (CsA), an inhibitor of CypA, inhibits this interaction and suppresses HCV replication. Mutations that confer resistance to CsA and derivatives have been identified within NS5A-DII (D320E and Y321N in Con 1b). These mutations revive HCV replication in vivo, but the underlying mechanism for resistance remains elusive. Using a Förster Resonance Energy Transfer (FRET)-based approach, we determined a slower rate of dissociation of the resistant NS5A-DII complex with CypA, in the presence of CsA. The slow complex dissociation directly correlated with the increasing level of resistance conferred by either single or double mutations within NS5A-DII. By prolonging the protein-protein complex, D320E and Y321N specifically limit the inhibitory effect of CsA on the NS5A-DII complex with CypA, providing a possible biochemical mechanism of resistance to CypA inhibitors. Apart from its CypA binding properties, NS5A-DII also binds RNA, and interacts with the HCV RNA-dependent RNA polymerase NS5B. However, the largely disordered nature of NS5A-DII has limited the characterization of the structure and functional relevance of these interactions. A mass spectrometry (MS)-assisted foot-printing approach provided an in-depth biochemical characterization of the molecular determinants of protein-protein and nucleoprotein interactions of HCV NS5A-DII with CypA, NS5B and RNA. Overlapping but definitive binding sites for each of the three macromolecules were determined. The conserved residue W316 was identified as a principle mediator of protein-protein interaction (CypA and NS5B) while an arginine-rich region of NS5A-DII was crucial for RNA binding. Specifically, NS5A-DII K308 residue was indispensable for RNA-binding. A novel binding site of NS5A-DII on the NS5B polymerase was mapped predominantly to a region associated with RNA binding. Additionally, binding of NS5A-DII diminished the RNA binding and RNA synthesis activity of NS5B polymerase. This implies a potential regulatory function of NS5A-DII on NS5B polymerase activity. Taken together, this work pinpoints key residues in the intrinsically disordered NS5A-DII that necessitate specific viral and host interactions. NS5A-DII has been plucked from obscurity as we begin to understand the biochemical functional relevance for these interactions, and their significance to HCV replication." --
Author :National Academies of Sciences, Engineering, and Medicine Publisher :National Academies Press ISBN 13 :0309438020 Total Pages :187 pages Book Rating :4.3/5 (94 download)
Book Synopsis Eliminating the Public Health Problem of Hepatitis B and C in the United States by : National Academies of Sciences, Engineering, and Medicine
Download or read book Eliminating the Public Health Problem of Hepatitis B and C in the United States written by National Academies of Sciences, Engineering, and Medicine and published by National Academies Press. This book was released on 2016-06-01 with total page 187 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hepatitis B and C cause most cases of hepatitis in the United States and the world. The two diseases account for about a million deaths a year and 78 percent of world's hepatocellular carcinoma and more than half of all fatal cirrhosis. In 2013 viral hepatitis, of which hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most common types, surpassed HIV and AIDS to become the seventh leading cause of death worldwide. The world now has the tools to prevent hepatitis B and cure hepatitis C. Perfect vaccination could eradicate HBV, but it would take two generations at least. In the meantime, there is no cure for the millions of people already infected. Conversely, there is no vaccine for HCV, but new direct-acting antivirals can cure 95 percent of chronic infections, though these drugs are unlikely to reach all chronically-infected people anytime soon. This report, the first of two, examines the feasibility of hepatitis B and C elimination in the United States and identifies critical success factors. The phase two report will outline a strategy for meeting the elimination goals discussed in this report.
Book Synopsis Viral Proteases and Their Inhibitors by : Satya Prakash Gupta
Download or read book Viral Proteases and Their Inhibitors written by Satya Prakash Gupta and published by Academic Press. This book was released on 2017-07-03 with total page 518 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral Proteases and Their Inhibitors provides a thorough examination of viral proteases from their molecular components, to therapeutic applications. As information on three dimensional structures and biological functions of these viral proteases become known, unexpected protein folds and unique mechanisms of proteolysis are realized. This book investigates how this facilitates the design and development of potent antiviral agents used against life-threatening viruses. Users will find descriptions of each virus that detail the structure and function of viral proteases, discuss the design and development of inhibitors, and analyze the structure-activity relationships of inhibitors. This book is ideal biochemists, virologists and those working on antiviral agents. Provides comprehensive, state-of-the-art coverage of virus infections, the virus lifecycle, and mechanisms of protease inhibition Analyzes structure-activity relationships of inhibitors of each viral protease Presents an in-depth view of the structure and function of viral proteases
