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Entry Inhibitors
Entry inhibitors, also known as fusion inhibitors, are a class of antiviral drugs that prevent a virus from entering a cell, for example, by blocking a receptor. Entry inhibitors are used to treat conditions such as HIV and hepatitis D. HIV entry They are used in combination therapy for the treatment of HIV infection. This class of drugs interferes with the binding, fusion and entry of an HIV virion to a human cell. By blocking this step in HIV's replication cycle, such agents slow the progression from HIV infection to AIDS. Proteins There are several key proteins involved in the HIV entry process. * CD4, a protein receptor found on the surface of helper T cells in the human immune system, also called CD4+ T cells * gp120, a protein on HIV surface that binds to the CD4 receptor * CCR5, a second receptor found on the surface of CD4+ cells and macrophages, called a chemokine co-receptor * CXCR4, another chemokine co-receptor found on CD4+ cells * gp41, a HIV protein, closely as ...
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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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Cell Membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the extracellular space). The cell membrane consists of a lipid bilayer, made up of two layers of phospholipids with cholesterols (a lipid component) interspersed between them, maintaining appropriate membrane fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that span the membrane and serve as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes to facilitate interaction with the cell's environment. Glycolipids embedded in the outer lipid layer serve a similar purpose. The cell membrane controls the movement of substances in and out of cells and organelles, being selectively permeable to ions a ...
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Green Tea
Green tea is a type of tea that is made from '' Camellia sinensis'' leaves and buds that have not undergone the same withering and oxidation process which is used to make oolong teas and black teas. Green tea originated in China, and since then its production and manufacture has spread to other countries in East Asia. Several varieties of green tea exist, which differ substantially based on the variety of ''C. sinensis'' used, growing conditions, horticultural methods, production processing, and time of harvest. The two main components unique to green tea are "catechins" and "theanine," and the health effects of these components are attracting a great deal of attention in Japan and abroad. History Tea consumption has its legendary origins in China during the reign of mythological Emperor Shennong. A book written by Lu Yu in 618–907 AD (Tang dynasty), ''The Classic of Tea'' (), is considered important in green tea history. The ''Kissa Yōjōki'' (喫茶養生記 ''Book ...
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Epigallocatechin Gallate
Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is the ester of epigallocatechin and gallic acid, and is a type of catechin. EGCG – the most abundant catechin in tea – is a polyphenol under basic research for its potential to affect human health and disease. EGCG is used in many dietary supplements. Food sources Tea It is found in high content in the dried leaves of green tea (7380 mg per 100 g), white tea (4245 mg per 100 g), and in smaller quantities, black tea (936 mg per 100 g). During black tea production, the catechins are mostly converted to theaflavins and thearubigins via polyphenol oxidases. Other Trace amounts are found in apple skin, plums, onions, hazelnuts, pecans, and carob powder (at 109 mg per 100 g). Bioavailability When taken orally, EGCG has poor absorption even at daily intake equivalent to 8–16 cups of green tea, an amount causing adverse effects such as nausea or heartburn. After consumption, EGCG ...
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Plerixafor
Plerixafor (INN and USAN, trade name Mozobil) is an immunostimulant used to mobilize hematopoietic stem cells in cancer patients into the bloodstream. The stem cells are then extracted from the blood and transplanted back to the patient. The drug was developed by AnorMED, which was subsequently bought by Genzyme. Medical uses Peripheral blood stem cell mobilization, which is important as a source of hematopoietic stem cells for transplantation, is generally performed using granulocyte colony-stimulating factor (G-CSF), but is ineffective in around 15 to 20% of patients. Combination of G-CSF with plerixafor increases the percentage of persons that respond to the therapy and produce enough stem cells for transplantation. The drug is approved for patients with lymphoma and multiple myeloma. Phase 2 clinical trials started in 2021 exploring the combination of plerixafor and MGTA-145, a CXCL2 ligand. Contraindications Pregnancy and lactation Studies in pregnant animals have shown ...
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Leronlimab
Leronlimab (codenamed PRO 140) is a humanized monoclonal antibody targeted against the CCR5 receptor found on T lymphocytes of the human immune system. It is being investigated as a potential therapy in the treatment of COVID-19, triple negative breast cancer, and HIV infection. The United States Food and Drug Administration has designated PRO 140 for fast-track approval. In February 2008, the drug entered Phase 2 clinical trials and a phase 3 trial was begun in 2015. In February 2018, Cytodyn Inc reported that the primary endpoint had been achieved in the PRO 140 pivotal combination therapy trial in HIV infection. In 2020 CytoDyn submitted a fast-track biologics license application for treatment of CCR5-tropic HIV-1 Infection. Development PRO 140 is being developed by Cytodyn Inc. In May 2007, results from the phase I clinical trial of the drug demonstrated "potent, rapid, prolonged, dose-dependent, highly significant antiviral activity" for PRO 140. Participants in the high ...
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Merck Manual
''The Merck Manual of Diagnosis and Therapy'', referred to as ''The Merck Manual'', is the world's best-selling medical textbook, and the oldest continuously published English language medical textbook. First published in 1899, the current print edition of the book, the 20th Edition, was published in 2018. In 2014, Merck decided to move ''The Merck Manual'' to digital-only, online publication, available in both professional and consumer versions; this decision was reversed in 2017, with the publication of the 20th edition the following year. ''The Merck Manual of Diagnosis and Therapy'' is one of several medical textbooks, collectively known as ''The Merck Manuals'', which are published by Merck Publishing, a subsidiary of the pharmaceutical company Merck Co., Inc. in the United States and Canada, and MSD (as ''The MSD Manuals'') in other countries in the world. Merck also formerly published ''The Merck Index'', ''An Encyclopedia of Chemicals, Drugs, and Biologicals.'' History an ...
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Fostemsavir
Fostemsavir, sold under the brand name Rukobia, is an antiretroviral medication for adults living with HIV/AIDS who have tried multiple HIV medications and whose HIV infection cannot be successfully treated with other therapies because of resistance, intolerance or safety considerations. The most common adverse reaction is nausea. Severe adverse reactions included elevations in liver enzymes among participants also infected with hepatitis B or C virus, and changes in the immune system (immune reconstitution syndrome). Fostemsavir is an HIV entry inhibitor and a prodrug of temsavir (BMS-626529). Fostemsavir is a human immunodeficiency virus type 1 (HIV-1) gp120-directed attachment inhibitor. It was approved for medical use in the United States in July 2020, and in the European Union in February 2021. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical uses Fostemsavir in combination with other antiretroviral(s), is indicated for ...
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Monoclonal Antibody
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 therapy ...
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Ibalizumab
Ibalizumab, sold under the brand name Trogarzo, is a non-immunosuppressive humanised monoclonal antibody that binds CD4, the primary receptor for HIV, and inhibits HIV from entering cells. It is a post-attachment inhibitor, blocking HIV from binding to the CCR5 and CXCR4 co-receptors after HIV binds to the CD4 receptor on the surface of a CD4 cell. Post-attachment inhibitors are a subclass of HIV drugs called entry inhibitors. On March 6, 2018, the U.S. Food and Drug Administration (FDA) approved ibalizumab for multidrug-resistant HIV-1. It is used in combination with other antiretroviral drugs. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical uses Ibalizumab, in combination with other antiretrovirals, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Development Ibalizumab is being developed by TaiMed Biologics but was originally developed by Tanox, now part of Genentech. As part of ...
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Enfuvirtide
Enfuvirtide (INN) is an HIV fusion inhibitor, the first of a class of antiretroviral drugs used in combination therapy for the treatment of HIV-1 infection. It is marketed under the trade name Fuzeon (Roche). Structural formula Enfuvirtide is a 36-amino acid peptide with the following sequence: CH3CO- Tyr- Thr-Ser- Leu-Ile-His-Ser-Leu-Ile- Glu-Glu-Ser- Gln- Asn-Gln-Gln-Glu- Lys-Asn-Glu-Gln-Glu-Leu-Leu-Glu-Leu- Asp- Lys- Trp-Ala-Ser-Leu-Trp- Asn-Trp- Phe- NH2 (Ac-YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF-NH2) History Enfuvirtide originated at Duke University, where researchers formed a pharmaceutical company known as Trimeris. Trimeris began development on enfuvirtide in 1996 and initially designated it T-20. In 1999, Trimeris entered into partnership with Hoffmann-La Roche to complete the development of the drug. It was approved by the U.S. Food and Drug Administration (FDA) on March 13, 2003 as the first HIV fusion inhibitor, a new class of antiretroviral drugs. It was approved ...
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Maraviroc
Maraviroc, sold under the brand names Selzentry (US) and Celsentri (EU), is an antiretroviral medication used to treat HIV infection. It is taken by mouth. It is in the CCR5 receptor antagonist class. It was approved for medical use in the United States in August 2007, and in the European Union in September 2007. Medical uses Maraviroc is indicated, in combination with other antiretroviral medications, for the treatment of only CCR5-tropic HIV-1 infection. Side effects Maraviroc can cause serious, life-threatening side effects. These include liver problems, skin reactions, and allergic reactions. An allergic reaction may happen before liver problems occur. Official labeling of Selzentry has black box warning for hepatotoxicity. The MOTIVATE trials showed no clinically relevant differences in safety between the maraviroc and placebo groups. Mechanism of action Maraviroc is an entry inhibitor. Specifically, maraviroc is a negative allosteric modulator of the CCR5 receptor, which ...
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