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COVID-19 Drug Repurposing Research
Drug repositioning (also known as drug repurposing, re-profiling, re-tasking, or therapeutic switching) is the repurposing of an approved drug for the treatment of a different disease or medical condition than that for which it was originally developed. This is one line of scientific research which is being pursued to develop safe and effective COVID-19 treatments. Other research directions include the development of a COVID-19 vaccine and convalescent plasma transfusion. Several existing antiviral medications, previously developed or used as treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV/AIDS, and malaria, have been researched as potential COVID-19 treatments, with some moving into clinical trials. In a statement to the journal '' Nature Biotechnology'' in February 2020, US National Institutes of Health Viral Ecology Unit chief Vincent Munster said, "The general genomic layout and the general replication kinetics ...
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Drug Repositioning
Drug repositioning (also called drug repurposing) involves the investigation of existing drugs for new therapeutic purposes. Repurposing achievements Repurposing generics can have groundbreaking effects for patients: 35% of 'transformative' drugs approved by the US FDA are repurposed products. Repurposing is especially relevant for rare or neglected diseases. A number of successes have been achieved, the foremost including sildenafil (Viagra) for erectile dysfunction and pulmonary hypertension and thalidomide for leprosy and multiple myeloma. Clinical trials have been performed on posaconazole and ravuconazole for Chagas disease. Other antifungal agents clotrimazole and ketoconazole have been investigated for anti- trypanosome therapy. Successful repositioning of antimicrobials has led to the discovery of broad-spectrum therapeutics, which are effective against multiple infection types. Strategy Drug repositioning is a "universal strategy" for neglected diseases due to ...
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The New York Times
''The New York Times'' (''NYT'') is an American daily newspaper based in New York City. ''The New York Times'' covers domestic, national, and international news, and publishes opinion pieces, investigative reports, and reviews. As one of the longest-running newspapers in the United States, the ''Times'' serves as one of the country's Newspaper of record, newspapers of record. , ''The New York Times'' had 9.13 million total and 8.83 million online subscribers, both by significant margins the List of newspapers in the United States, highest numbers for any newspaper in the United States; the total also included 296,330 print subscribers, making the ''Times'' the second-largest newspaper by print circulation in the United States, following ''The Wall Street Journal'', also based in New York City. ''The New York Times'' is published by the New York Times Company; since 1896, the company has been chaired by the Ochs-Sulzberger family, whose current chairman and the paper's publ ...
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Antibody
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, including those that cause disease. Each individual antibody recognizes one or more specific antigens, and antigens of virtually any size and chemical composition can be recognized. Antigen literally means "antibody generator", as it is the presence of an antigen that drives the formation of an antigen-specific antibody. Each of the branching chains comprising the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" the antigen (or a microbe or an infected cell bearing such an antigen) for attack by cells of the immune system, or can neutralize it directly (for example, by blocking a p ...
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Mavrilimumab
Mavrilimumab is a human monoclonal antibody that inhibits human granulocyte macrophage colony-stimulating factor receptor (GM-CSF-R). Mavrilimumab was discovered as CAM-3001 by Cambridge Antibody Technology and is being developed by MedImmune, Inc. as an investigational drug for the treatment of rheumatoid arthritis Mavrilimumab has been studied in a phase 1 dose-ranging trial and a phase 2a clinical trial, both sponsored by Medimmune. The phase 2a trial, which studied mavrilimumab doses of up to 100 mg, reported that 55.7% of subjects met the primary endpoint of a ≥1.2 decrease from baseline in disease activity scores at week 12 (vs. only 34.7% of placebo subjects). In 2013, two further clinical studies were reported to be underway in rheumatoid arthritis patients to investigate these effects further. In early 2017 the phase IIb study was reported to be showing promising results. In 2017, Kiniksa licensed Mavrilimumab from MedImmune. It was studied in 2020 to see ...
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COVID-19 Drug Development
COVID-19 drug development is the research process to develop preventative therapeutic prescription drugs that would alleviate the severity of coronavirus disease 2019 (COVID-19). From early 2020 through 2021, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of preclinical or clinical research (506 total candidates in April 2021), with 419 potential COVID-19 drugs in clinical trials, as of April 2021. As early as March 2020, the World Health Organization (WHO), European Medicines Agency (EMA), US Food and Drug Administration (FDA), and the Chinese government and drug manufacturers were coordinating with academic and industry researchers to speed development of vaccines, antiviral drugs, and post-infection therapies. The International Clinical Trials Registry Platform of the WHO recorded 536 clinical studies to develop post-infection therapies f ...
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Interleukin 8
Interleukin 8 (IL-8 or chemokine (C-X-C motif) ligand 8, CXCL8) is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel–Palade bodies. In humans, the interleukin-8 protein is encoded by the ''CXCL8'' gene. IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms. In culture, a 72 amino acid peptide is the major form secreted by macrophages. There are many receptors on the surface membrane capable of binding IL-8; the most frequently studied types are the G protein-coupled serpentine receptors CXCR1 and CXCR2. Expression and affinity for IL-8 differs between the two receptors (CXCR1 > CXCR2). Through a chain of biochemical reactions, IL-8 is secreted and is an important mediator of the immune reaction in the innate immune system response. Functio ...
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Tocilizumab
Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, cytokine release syndrome, COVID19, and systemic sclerosis-associated interstitial lung disease (SSc-ILD). It is a recombinant humanized monoclonal antibody of the immunoglobulin IgG1 subclass against the interleukin-6 receptor (IL-6R). Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche. Tocilizumab was approved for medica ...
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Anti-IL-6
Anti-interleukin-6 agents are a class of therapeutics. Interleukin 6 is a cytokine relevant to many inflammatory diseases and many cancers. Hence, anti-IL6 agents have been sought. In rheumatoid arthritis they can help patients unresponsive to TNF inhibitors. The first approved medication in this class, tocilizumab (Actemra), is an antibody directed against the IL6-receptor. The second, siltuximab (Sylvant), is directed against IL-6 itself. Siltuximab is approved for treatment of human immunodeficiency virus-negative and HHV-8-negative patients with multicentric Castleman's disease. Siltuximab was also tested in the phase I/II study for therapy of patients with metastatic castration-associated prostate cancer in combination with docetaxel and in renal cell carcinoma; phase II trials in ovarian cancer resulted in 39% of patients showed disease stabilization via IL-6-regulated downregulation of CCL2, CXCL12 and VEGF. Tocilizumab was first used in large-cell lung carcinoma. In ...
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Monoclonal Antibodies
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a Lineage (evolution), cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies are identical and can thus have Valence (chemistry), monovalent affinity, binding only to a particular epitope (the part of an antigen that is recognized by the antibody). In contrast, polyclonal antibodies are mixtures of antibodies derived from multiple plasma cell lineages which each bind to their particular target epitope. Artificial antibodies known as bispecific monoclonal antibodies can also be engineered which include two different antigen binding sites (Fragment antigen-binding region, FABs) on the same antibody. It is possible to produce monoclonal antibodies that specifically bind to almost any suitable substance; they can then serve to detect or purify it. This capability has become an investigative tool in b ...
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Meta-analysis
Meta-analysis is a method of synthesis of quantitative data from multiple independent studies addressing a common research question. An important part of this method involves computing a combined effect size across all of the studies. As such, this statistical approach involves extracting effect sizes and variance measures from various studies. By combining these effect sizes the statistical power is improved and can resolve uncertainties or discrepancies found in individual studies. Meta-analyses are integral in supporting research grant proposals, shaping treatment guidelines, and influencing health policies. They are also pivotal in summarizing existing research to guide future studies, thereby cementing their role as a fundamental methodology in metascience. Meta-analyses are often, but not always, important components of a systematic review. History The term "meta-analysis" was coined in 1976 by the statistician Gene V. Glass, Gene Glass, who stated ''"Meta-analysis refers t ...
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Base Rate Fallacy
The base rate fallacy, also called base rate neglect or base rate bias, is a type of fallacy in which people tend to ignore the base rate (e.g., general prevalence) in favor of the individuating information (i.e., information pertaining only to a specific case). For example, if someone hears that a friend is very shy and quiet, they might think the friend is more likely to be a librarian than a salesperson. However, there are far more salespeople than librarians overall—hence making it more likely that their friend is actually a salesperson, even if a greater proportion of librarians fit the description of being shy and quiet. Base rate neglect is a specific form of the more general extension neglect. It is also called the prosecutor's fallacy or defense attorney's fallacy when applied to the results of statistical tests (such as DNA tests) in the context of law proceedings. These terms were introduced by William C. Thompson and Edward Schumann in 1987, although it has been arg ...
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Type I Error
Type I error, or a false positive, is the erroneous rejection of a true null hypothesis in statistical hypothesis testing. A type II error, or a false negative, is the erroneous failure in bringing about appropriate rejection of a false null hypothesis. Type I errors can be thought of as errors of commission, in which the status quo is erroneously rejected in favour of new, misleading information. Type II errors can be thought of as errors of omission, in which a misleading status quo is allowed to remain due to failures in identifying it as such. For example, if the assumption that people are ''innocent until proven guilty'' were taken as a null hypothesis, then proving an innocent person as guilty would constitute a Type I error, while failing to prove a guilty person as guilty would constitute a Type II error. If the null hypothesis were inverted, such that people were by default presumed to be ''guilty until proven innocent'', then proving a guilty person's innocence would ...
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