Harvoni
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Harvoni
Ledipasvir/sofosbuvir, sold under the trade name Harvoni among others, is a medication used to treat hepatitis C. It is a fixed-dose combination of ledipasvir and sofosbuvir. Cure rates are 94% to 99% in people infected with hepatitis C virus (HCV) genotype 1. Some evidence also supports use in HCV genotype 3 and 4. It is taken daily by mouth for 8–24 weeks. It is generally well tolerated. Common side effects include muscle pains, headache, nausea, rash, and cough. It is unclear if use in pregnancy is safe for the baby. Ledipasvir works by decreasing the activity of NS5A and sofosbuvir works by decreasing the activity of NS5B polymerase. Ledipasvir/sofosbuvir was approved for medical use in the United States, in the European Union, and in Canada in 2014. It is on the World Health Organization's List of Essential Medicines. Medical uses Cure rates are 94% to 99% in people infected with genotype 1 (46% of HCV cases). It has also been evaluated for the treatment of infection ...
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Ledipasvir
Ledipasvir is a drug for the treatment of hepatitis C that was developed by Gilead Sciences. After completing Phase III clinical trials, on February 10, 2014, Gilead filed for U.S. approval of a ledipasvir/sofosbuvir fixed-dose combination tablet for genotype 1 hepatitis C. The ledipasvir/sofosbuvir combination is a direct-acting antiviral agent that interferes with HCV replication and can be used to treat patients with genotypes 1a or 1b without PEG-interferon or ribavirin. Ledipasvir is an inhibitor of NS5A, a hepatitis C virus protein. Data presented at the 20th Conference on Retroviruses and Opportunistic Infections in March 2013 showed that a triple regimen of the nucleotide analog inhibitor sofosbuvir, ledipasvir, and ribavirin produced a 12-week post-treatment sustained virological response (SVR12) rate of 100% for both treatment-naive patients and prior non-responders with HCV genotype 1. The sofosbuvir/ledipasvir coformulation is being tested with and without ribavir ...
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Sofosbuvir
Sofosbuvir, sold under the brand name Sovaldi among others, is a medication used to treat hepatitis C. It is taken Oral administration, by mouth. Common side effects include fatigue, headache, nausea, and trouble sleeping. Side effects are generally more common in interferon-containing regimens. Sofosbuvir may reactivate hepatitis B in those who have been previously infected. In combination with ledipasvir, daclatasvir or simeprevir, it is not recommended with amiodarone due to the risk of an bradycardia, abnormally slow heartbeat. Sofosbuvir is in the nucleotide analog family of medications and works by blocking the hepatitis C NS5B protein. Sofosbuvir was discovered in 2007 and approved for medical use in the United States in 2013. It is on the WHO Model List of Essential Medicines, World Health Organization's List of Essential Medicines. Medical uses Initial HCV treatment In 2016, the American Association for the Study of Liver Diseases and the Infectious Diseases ...
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NS5B
Nonstructural protein 5B (NS5B) is a viral protein found in the hepatitis C virus (HCV). It is an RNA-dependent RNA polymerase, having the key function of replicating HCV's viral RNA by using the viral positive RNA strand as a template to catalyze the polymerization of ribonucleoside triphosphates (rNTP) during RNA replication. Several crystal structures of NS5B polymerase in several crystalline forms have been determined based on the same consensus sequence BK (HCV-BK, genotype 1). The structure can be represented by a right hand shape with fingers, palm, and thumb. The encircled active site, unique to NS5B, is contained within the palm structure of the protein. Recent studies on NS5B protein genotype 1b strain J4's (HC-J4) structure indicate a presence of an active site where possible control of nucleotide binding occurs and initiation of de-novo RNA synthesis. De-novo adds necessary primers for initiation of RNA replication. Drugs targeting NS5B Several drugs are either on the ma ...
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NS5B Polymerase
Nonstructural protein 5B (NS5B) is a viral protein found in the hepatitis C virus (HCV). It is an RNA-dependent RNA polymerase, having the key function of replicating HCV's viral RNA by using the viral positive RNA strand as a template to catalyze the polymerization of ribonucleoside triphosphates (rNTP) during RNA replication. Several crystal structures of NS5B polymerase in several crystalline forms have been determined based on the same consensus sequence BK (HCV-BK, genotype 1). The structure can be represented by a right hand shape with fingers, palm, and thumb. The encircled active site, unique to NS5B, is contained within the palm structure of the protein. Recent studies on NS5B protein genotype 1b strain J4's (HC-J4) structure indicate a presence of an active site where possible control of nucleotide binding occurs and initiation of de-novo RNA synthesis. De-novo adds necessary primers for initiation of RNA replication. Drugs targeting NS5B Several drugs are either on the ma ...
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H2 Receptor Antagonists
H2 antagonists, sometimes referred to as H2RAs and also called H2 blockers, are a class of medications that block the action of histamine at the histamine H2 receptors of the parietal cells in the stomach. This decreases the production of stomach acid. H2 antagonists can be used in the treatment of dyspepsia, peptic ulcers and gastroesophageal reflux disease. They have been surpassed by proton pump inhibitors (PPIs); the PPI omeprazole was found to be more effective at both healing and alleviating symptoms of ulcers and reflux oesophagitis than the H2 blockers ranitidine and cimetidine. H2 antagonists are a type of antihistamine, although in common use the term "antihistamine" is often reserved for H1 antagonists, which relieve allergic reactions. Like the H1 antagonists, some H2 antagonists function as inverse agonists rather than receptor antagonists, due to the constitutive activity of these receptors. The prototypical H2 antagonist, called cimetidine, was developed by Si ...
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Proton-pump Inhibitor
Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump. They are the most potent inhibitors of acid secretion available. Proton-pump inhibitors have largely superseded the H2-receptor antagonists, a group of medications with similar effects but a different mode of action, and antacids. PPIs are among the most widely sold medications in the world. The class of proton-pump inhibitor medications is on the World Health Organization's List of Essential Medicines. Omeprazole is the specific listed example. Medical uses These medications are used in the treatment of many conditions, such as: * Dyspepsia * Peptic ulcer disease including after endoscopic treatment for bleeding * As part of ''Helicobacter pylori'' eradication therapy * Gastroesophageal reflux disease (GERD or GORD) including symptomatic endoscopy-negative reflux disea ...
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Amiodarone
Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibrillation and paroxysmal supraventricular tachycardia. Evidence in cardiac arrest, however, is poor. It can be given by mouth, intravenously, or intraosseously. When used by mouth, it can take a few weeks for effects to begin. Common side effects include feeling tired, tremor, nausea, and constipation. As amiodarone can have serious side effects, it is mainly recommended only for significant ventricular arrhythmias. Serious side effects include lung toxicity such as interstitial pneumonitis, liver problems, heart arrhythmias, vision problems, thyroid problems, and death. If taken during pregnancy or breastfeeding it can cause problems in the fetus. It is a class III antiarrhythmic medication. It works partly by increasing the time before a he ...
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Bradycardia
Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, and in athletes. In some people, bradycardia below 60 BPM may be associated with fatigue, weakness, dizziness, sweating, and fainting. The term "relative bradycardia" is used to refer to a heart rate slower than an individual's typical resting heart rate. Athletes may have athletic heart syndrome, which includes bradycardia as part of the cardiovascular adaptations to training and participation. The word "bradycardia" is from the Greek βραδύς ''bradys'' "slow", and καρδία ''kardia'' "heart". Classification Sinus Atrial bradycardias are divided into three types. The first, respiratory sinus arrhythmia, is usually found in young and healthy adults. Heart rate increases during inhalation and decreases during exhalation. Thi ...
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Hyperphosphorylation
Hyperphosphorylation occurs when a biochemical with multiple phosphorylation sites is fully saturated. Hyperphosphorylation is one of the signaling mechanisms used by the cell to regulate mitosis. When these mechanisms fail, developmental problems or cancer are a likely outcome. The mechanism appears to be largely conserved throughout eukaryote species. The dynamics of mitosis are similar to a state machine. In a healthy cell, checkpoints between phases permit a new phase to begin only when the previous phase is complete and successful. At these checkpoints, gatekeeper molecules block or allow events, depending on their level of phosphorylation. Kinases are responsible for adding phosphate groups and phosphatases for removing them. Cyclins are molecules that manage the timing of cell cycle events. Cyclin dependent kinases pair up with cyclins to become operational. Cyclins are named because they are created or destroyed at predetermined points within the cell cycle. Kinase inhi ...
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NS5A
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 ...
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De Novo Transcriptome Assembly
''De novo'' transcriptome assembly is the de novo sequence assembly method of creating a transcriptome without the aid of a reference genome. Introduction As a result of the development of novel sequencing technologies, the years between 2008 and 2012 saw a large drop in the cost of sequencing. Per megabase and genome, the cost dropped to 1/100,000th and 1/10,000th of the price, respectively. Prior to this, only transcriptomes of organisms that were of broad interest and utility to scientific research were sequenced; however, these developed in 2010s high-throughput sequencing (also called next-generation sequencing) technologies are both cost- and labor- effective, and the range of organisms studied via these methods is expanding. Transcriptomes have subsequently been created for chickpea, planarians, '' Parhyale hawaiensis'', as well as the brains of the Nile crocodile, the corn snake, the bearded dragon, and the red-eared slider, to name just a few. Examining non-model organ ...
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Rifampicin
Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), mycobacterium avium complex, ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. It is almost always used together with other antibiotics with two notable exceptions: when given as a "preferred treatment that is strongly recommended" for latent TB infection; and when used as post-exposure prophylaxis to prevent Haemophilus influenzae type b, ''Haemophilus influenzae'' type b and meningococcal disease in people who have been exposed to those bacteria. Before treating a person for a long period of time, measurements of liver enzymes and blood counts are recommended. Rifampicin may be given either Oral administration, by mouth or intravenously. Common side effects include nausea, vomiting, diarrhea, and loss of appetite. It often turns urine, sweat, and tears a red or orange color. Liver problems or allergic reactions ma ...
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