Beclabuvir
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Beclabuvir
Beclabuvir (also known by the research name BMS-791325; abbreviated BCV) is an antiviral drug for the treatment of hepatitis C virus (HCV) infection that has been studied in clinical trials. In February 2017, Bristol-Myers Squibb began sponsoring a post-marketing trial of beclabuvir, in combination with asunaprevir and daclatasvir, to study the combination's safety profile with regard to liver function. From February 2014 to November 2016, a phase II clinical trial was conducted on the combination of asunaprevir/daclatasvir/beclabuvir (beclabuvir is referred to as BMS-791325 in the trial) on patients infected with both HIV and HCV. Furthermore, a recent meta-analysis of six published six clinical trials showed high response rates in HCV genotype 1-infected patients treated with daclatasvir, asunaprevir, and beclabuvir irrespective of ribavirin use, prior interferon-based therapy, or restriction on noncirrhotic patients, IL28B genotype, or baseline resistance-associated variants ...
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Bristol-Myers Squibb
The Bristol Myers Squibb Company (BMS) is an American multinational pharmaceutical company. Headquartered in New York City, BMS is one of the world's largest pharmaceutical companies and consistently ranks on the ''Fortune'' 500 list of the largest U.S. corporations. For fiscal 2021, it had a total revenue of $46.4 billion. Bristol Myers Squibb manufactures prescription pharmaceuticals and biologics in several therapeutic areas, including cancer, HIV/AIDS, cardiovascular disease, diabetes, hepatitis, rheumatoid arthritis, and psychiatric disorders. BMS's primary research and development (R&D) sites are located in Lawrence, New Jersey (formerly Squibb, near Princeton), Summit, New Jersey, formerly HQ of Celgene, New Brunswick, New Jersey, Redwood City, California, and Seville in Spain, with other sites in Devens and Cambridge, Massachusetts, East Syracuse, New York, Braine-l'Alleud, Belgium, Tokyo, Japan, Bangalore, India, and Wirral, United Kingdom. BMS previously had ...
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Hepatitis C Virus
The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepatocellular carcinoma, abbreviated HCC) and lymphomas in humans. Taxonomy The hepatitis C virus belongs to the genus ''Hepacivirus'', a member of the family ''Flaviviridae''. Before 2011, it was considered to be the only member of this genus. However a member of this genus has been discovered in dogs: canine hepacivirus. There is also at least one virus in this genus that infects horses. Several additional viruses in the genus have been described in bats and rodents. Structure The hepatitis C virus particle consists of a lipid membrane envelope that is 55 to 65 nm in diameter. Two viral envelope glycoproteins, E1 and E2, are embedded in the lipid envelope. They take part in viral attachment and entry into the cell. Within the envel ...
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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) Inhibitors
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 RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template. This is in contrast to t .... 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 ...
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Antiviral Drug
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit its development. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic (also termed antibacterial), antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from viricides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural viricides are produced by some plants such as eucalyptus and Australian tea trees. Medical uses Most of the antiviral drugs now available are designed to help deal with HIV, herpes viruses, th ...
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Clinical Trials
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small pilot studies, and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary i ...
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Asunaprevir
Asunaprevir (formerly BMS-650032, brand name in Japan and Russia Sunvepra) is an experimental drug candidate for the treatment of hepatitis C. It was undergoing development by Bristol-Myers Squibb and has completed Phase III clinical trials in 2013. Asunaprevir is an inhibitor of the hepatitis C virus enzyme serine protease NS3. Asunaprevir is being tested in combination with pegylated interferon and ribavirin, as well as in interferon-free regimens with other direct-acting antiviral agents including daclatasvir.AASLD: Daclatasvir plus Asunaprevir Rapidly Suppresses HCV in Prior Null Responders
. Highleyman, L. HIVandHepatitis.com. 8 November 2011.


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Daclatasvir
Daclatasvir, sold under the brand name Daklinza, is an antiviral medication used in combination with other medications to treat hepatitis C (HCV). The other medications used in combination include sofosbuvir, ribavirin, and interferon, vary depending on the virus type and whether the person has cirrhosis. It is taken by mouth. Common side effects when used with sofusbivir and daclatasvir include headache, feeling tired, and nausea. With daclatasvir, sofosbuvir, and ribavirin the most common side effects are headache, feeling tired, nausea, and red blood cell breakdown. It should not be used with St. John's wort, rifampin, or carbamazepine. It works by inhibiting the HCV protein NS5A. Daclatasvir was approved for use in the European Union in 2014, and the United States and India in 2015. It is on the World Health Organization's List of Essential Medicines. The brand Daklinza is being withdrawn by Bristol Myers Squibb in countries where the drug is not typically prescribed, a ...
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Phase II Clinical Trial
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over sever ...
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Ribavirin
Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, peginterferon alfa-2b or peginterferon alfa-2a. Among the viral hemorrhagic fevers it is used for Lassa fever, Crimean–Congo hemorrhagic fever, and Hantavirus infection but should not be used for Ebola or Marburg infections. Ribavirin is taken by mouth or inhaled. Common side effects include feeling tired, headache, nausea, fever, muscle pains, and an irritable mood. Serious side effects include red blood cell breakdown, liver problems, and allergic reactions. Use during pregnancy results in harm to the baby. Effective birth control is recommended for both males and females for at least seven months during and after use. The mechanism of action of ribavirin is not entirely clear. Ribavirin was patented in 1971 and approved for medical us ...
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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 ...
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Non-cirrhotic Portal Fibrosis
Non-cirrhotic portal fibrosis (NCPF) is a chronic liver disease and type of non-cirrhotic portal hypertension (NCPH). Presentation It is characterized by 'obliterative portovenopathy', which leads to various problems such as portal hypertension, massive splenomegaly, and variceal bleeding. It is estimated that about 85% of people with NCPF have repeated episodes of variceal bleeding. Diagnosis Hallmark of the disease is thrombosis/ sclerosis of branches of portal vein. Vessels formed are often termed as mesangiosinusoids or periportal cavernoma Cavernous hemangioma, also called cavernous angioma, venous malformation, or cavernoma, is a type of venous malformation due to endothelial dysmorphogenesis from a lesion which is present at birth. A cavernoma in the brain is called a cerebral ca .... Treatment References External links Diseases of liver {{Disease-stub ...
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