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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 and the ...
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Drug Repositioning
Drug repositioning (also called drug repurposing) involves the investigation of existing drugs for new therapeutic purposes. Repurposing achievements 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. In psychiatry, repurposed drugs are emerging as feasible options to treat severe mental disorders. Strategy Drug repositioning is a "universal strategy" for neglected diseases due to 1) reduced number of required clinical trial steps could reduce the time and costs for the medicine to reach ...
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European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or European Medicines Evaluation Agency (EMEA).Set up by EC Regulation No. 2309/93 as the European Agency for the Evaluation of Medicinal Products, and renamed by EC Regulation No. 726/2004 to the European Medicines Agency, it had the acronym EMEA until December 2009. The European Medicines Agency does not call itself EMA either – it has no official acronym but may reconsider if EMA becomes commonly accepted (secommunication on new visual identity an). The EMA was set up in 1995, with funding from the European Union and the pharmaceutical industry, as well as indirect subsidy from member states, its stated intention to harmonise (but not replace) the work of existing national medicine regulatory bodies. The hope was that this plan would not o ...
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American Medical Association
The American Medical Association (AMA) is a professional association and lobbying group of physicians and medical students. Founded in 1847, it is headquartered in Chicago, Illinois. Membership was approximately 240,000 in 2016. The AMA's stated mission is "to promote the art and science of medicine and the betterment of public health." The Association also publishes the '' Journal of the American Medical Association'' (JAMA). The AMA also publishes a list of Physician Specialty Codes which are the standard method in the U.S. for identifying physician and practice specialties. The American Medical Association is governed by a House of Delegates as well as a board of trustees in addition to executive management. The organization maintains the AMA Code of Medical Ethics, and the AMA Physician Masterfile containing data on United States Physicians. The ''Current Procedural Terminology'' coding system was first published in 1966 and is maintained by the Association. It has also ...
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Granulocyte Macrophage Colony-stimulating Factor Receptor
The granulocyte-macrophage colony-stimulating factor receptor also known as CD116 (Cluster of Differentiation 116), is a receptor for granulocyte-macrophage colony-stimulating factor, which stimulates the production of white blood cells. In contrast to M-CSF and G-CSF which are lineage specific, GM-CSF and its receptor play a role in earlier stages of development. The receptor is primarily located on neutrophils, eosinophils and monocytes/macrophages, it is also on CD34+ progenitor cells (myeloblasts) and precursors for erythroid and megakaryocytic lineages, but only in the beginning of their development. It is associated with Surfactant metabolism dysfunction type 4. Structure The granulocyte-macrophage colony-stimulating factor receptor is a heterodimer composed of at least two different subunits; an α chain, and a β chain which is also present in the receptors for IL-3 and IL-5. The α subunit contains a binding site for granulocyte macrophage colony-stimulating factor, ...
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Antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can ''tag'' a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking a part of a virus that is essential for its invasion). To allow the immune system to recognize millions of different antigens, the antigen-binding sites at both tips of the antibody come in an equally wide variety. In contrast, the remainder of the antibody is relatively constant. It only occurs in a few vari ...
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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 i ...
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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 therapie ...
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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. Function IL- ...
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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, a severe form of arthritis in children, and COVID19. It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). 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 granted an emergency use authorization (EUA) for the treatment of COVID19 in the United States in June 2021. It was approved for the treatment of COVID19 in the European Union in December 2011, and in the United States in December 2022. Medical uses In the United States, tocilizumab is indicated for the treatment of rheumatoid arthritis ...
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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 ph ...
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Monoclonal Antibodies
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a 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 can have monovalent affinity, binding only to the same epitope (the part of an antigen that is recognized by the antibody). In contrast, polyclonal antibodies bind to multiple epitopes and are usually made by several different antibody-secreting plasma cell lineages. Bispecific monoclonal antibodies can also be engineered, by increasing the therapeutic targets of one monoclonal antibody to two epitopes. It is possible to produce monoclonal antibodies that specifically bind to virtually any suitable substance; they can then serve to detect or purify it. This capability has become an investigative tool in biochemistry, molecular biology, and medicine. Monoclonal antibodies are being used on a clinical level for both the diagnosis and thera ...
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Meta-analysis
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting measurements that are expected to have some degree of error. The aim then is to use approaches from statistics to derive a pooled estimate closest to the unknown common truth based on how this error is perceived. Meta-analytic results are considered the most trustworthy source of evidence by the evidence-based medicine literature.Herrera Ortiz AF., Cadavid Camacho E, Cubillos Rojas J, Cadavid Camacho T, Zoe Guevara S, Tatiana Rincón Cuenca N, Vásquez Perdomo A, Del Castillo Herazo V, & Giraldo Malo R. A Practical Guide to Perform a Systematic Literature Review and Meta-analysis. Principles and Practice of Clinical Research. 2022;7(4):47–57. https://doi.org/10.21801/ppcrj.2021.74.6 Not only can meta-analyses provide an estimate of the u ...
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