Odalasvir
Odalasvir (INN, previously known as ACH-3102) is an investigational new drug in development for the treatment of hepatitis C. It is an NS5A inhibitor. The NS5A protein serves multiple functions at various stages of the viral life cycle, including viral replication. NS5A also plays a role in the development of interferon-resistance, a common cause of treatment failure. It is under development by Achillion Pharmaceuticals. See also * Discovery and development of NS5A inhibitors Nonstructural protein 5A (NS5A) inhibitors are direct acting antiviral agents (DAAs) that target viral proteins, and their development was a culmination of increased understanding of the viral life cycle combined with advances in drug discovery te ... References Benzimidazoles Carbamates NS5A inhibitors Experimental drugs Cyclophanes {{antiinfective-drug-stub ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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NS5A Inhibitors
Nonstructural protein 5A (NS5A) is a zinc-binding and proline-rich hydrophilic phosphoprotein that plays a key role in Hepatitis C virus RNA replication. It appears to be a dimeric form without ''trans''-membrane helices. Structure NS5A is derived from a large polyprotein that is translated from the HCV genome, and undergoes post-translation processing by nonstructural protein 3 (NS3) viral protease. Despite no inherent enzymatic activity being attributed to NS5A, its function is mediated through interaction with other nonstructural (NS) viral and cellular proteins. NS5A has two phosphorylated forms: p56 and p58, which differ in the electrophoretic mobility. p56 is basally phosphorylated by host cellular protein kinase at the center and near the C terminus, whereas p58 is a form of hyper-phosphorylated NS5A at the center of the serine-rich region. Protein mass spectrometry identified several phosphorylated serine residues in this region including serine 225, 229, 232, and 235 res ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Hepatitis C
Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, abdominal pain, and yellow tinged skin occurs. The virus persists in the liver in about 75% to 85% of those initially infected. Early on, chronic infection typically has no symptoms. Over many years however, it often leads to liver disease and occasionally cirrhosis. In some cases, those with cirrhosis will develop serious complications such as liver failure, liver cancer, or dilated blood vessels in the esophagus and stomach. HCV is spread primarily by blood-to-blood contact associated with injection drug use, poorly sterilized medical equipment, needlestick injuries in healthcare, and transfusions. Using blood screening, the risk from a transfusion is less than one per two million. It may also be spread from an infected mother to her ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Discovery And Development Of NS5A Inhibitors
Nonstructural protein 5A (NS5A) inhibitors are direct acting antiviral agents (DAAs) that target viral proteins, and their development was a culmination of increased understanding of the viral life cycle combined with advances in drug discovery technology. However, their mechanism of action is complex and not fully understood. NS5A inhibitors were the focus of much attention when they emerged as a part of the first curative treatment for hepatitis C virus (HCV) infections in 2014. Favorable characteristics have been introduced through varied structural changes, and structural similarities between NS5A inhibitors that are clinically approved are readily apparent. Despite the recent introduction of numerous new antiviral drugs, resistance is still a concern and these inhibitors are therefore always used in combination with other drugs. Hepatitis C virus HCV is a positive-sense single-stranded RNA virus that has been demonstrated to replicate in the hepatocytes of both humans and chi ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Viral Life Cycle
Viruses are only able to Replicate (biology), replicate themselves by commandeering the reproductive apparatus of cells and making them reproduce the virus's genetic structure and virion, particles instead. How viruses do this depends mainly on the type of nucleic acid DNA or RNA they contain, which is either one or the other but never both. Viruses cannot function or reproduce outside a cell, and are totally dependent on a host cell (biology), cell to survive. Most viruses are species specific, and related viruses typically only infect a narrow range of plants, animals, bacteria, or fungi.N.J. Dimmock et al. ''Introduction to Modern Virology'', 6th edition. Blackwell Publishing, 2007. Life cycle process Viral entry For the virus to reproduce and thereby establish infection, it must enter cells of the host organism and use those cells' materials. To enter the cells, proteins on the surface of the virus interact with proteins of the cell. Attachment, or adsorption, occurs between ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Viral Replication
Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome and packaging these copies, the virus continues infecting new hosts. Replication between viruses is greatly varied and depends on the type of genes involved in them. Most DNA viruses assemble in the nucleus while most RNA viruses develop solely in cytoplasm. Viral production / replication Viruses multiply only in living cells. The host cell must provide the energy and synthetic machinery and the low- molecular-weight precursors for the synthesis of viral proteins and nucleic acids. The virus replication occurs in seven stages, namely; # Attachment # Entry, # Uncoating, # Transcription / mRNA production, # Synthesis of virus components, # Virion assembly and # Release (Liberation Stage). Attachment It is the first step of viral replication ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Interferon
Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses. IFNs belong to the large class of proteins known as cytokines, molecules used for communication between cells to trigger the protective defenses of the immune system that help eradicate pathogens. Interferons are named for their ability to "interfere" with viral replication by protecting cells from virus infections. However, virus-encoded genetic elements have the ability to antagonize the IFN response contributing to viral pathogenesis and viral diseases. IFNs also have various other functions: they activate immune cells, such as natural killer cells and macrophages, and they increase host defenses by up-regulating antigen presentation by virtue of increasing the expression of major histocompatibility complex (M ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Drug Development
Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for regulatory status, such as via the United States Food and Drug Administration for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug. The entire process – from concept through preclinical testing in the laboratory to clinical trial development, including Phase I–III trials – to approved vaccine or drug typically takes more than a decade. New chemical entity development Broadly, the process of drug development can be divided into preclinical and clinical work. Pre-clinical New chemical entities (NCEs, also known as new molecular entities or NMEs) are compounds that emerge from the process of drug discovery. Th ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Benzimidazoles
Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound may be viewed as fused rings of the aromatic compounds benzene and imidazole. It is a colorless solid. Preparation Benzimidazole is produced by condensation of o-phenylenediamine with formic acid,. or the equivalent trimethyl orthoformate: :C6H4(NH2)2 + HC(OCH3)3 → C6H4N(NH)CH + 3 CH3OH 2-substituted derivatives are obtained when the condensation is conducted with aldehydes in place of formic acid, followed by oxidation.Robert A. Smiley "Phenylene- and Toluenediamines" in Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim. Reactions Benzimidazole is a base: :C6H4N(NH)CH + H+ → 6H4(NH)2CHsup>+ It can also be deprotonated with stronger bases: :C6H4N(NH)CH + LiH → Li 6H4N2CH + H2 The imine can be alkylated and also serves as a ligand in coordination chemistry. The most prominent benzimidazole complex features ''N''-ribosyl-dimethylbenzimidazole as foun ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Carbamates
In organic chemistry, a carbamate is a category of organic compounds with the general formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formally obtained by replacing one or more of the hydrogen atoms by other organic functional groups; as well as salts with the carbamate anion (e.g. ammonium carbamate). Polymers whose units are joined by carbamate groups are an important family of plastics, the polyurethanes. Properties While carbamic acids are unstable, many carbamate esters or ionic) are stable and well known. Equilibrium with carbonate and bicarbonate In water solutions, the carbamate anion slowly equilibrates with the ammonium cation and the carbonate or bicarbonate anions: : : Calcium carbamate is soluble in water, whereas calcium carbonate is not. Adding a calcium salt to an ammonium carbamate/carbonate solution will precipitate some calcium carbonate immediately, a ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |