VIR-576
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VIR-576
VIR-576 is an experimental drug that is under clinical trials for the treatment of HIV-1 infections. VIR-576 is synthetic peptide that binds to HIV-1's hydrophobic fusion peptide gp41, preventing the virus from inserting itself into a host cell's membrane to initiate an infection. This drug is a synthesized variant of a highly specific natural entry inhibitor designated as VIRIP (virus-inhibitory peptide). The design of VIR-576 was based on VIRIP which in turn was discovered in 2007 by Frank Kirchhoff and coworkers. This product is being developed by VIRO Pharmaceuticals GmbH & Co. KG. Origins and development In 2007, a new natural peptide was discovered in the human organism and was called VIRIP. It is generated from Alpha 1-antitrypsin, alpha-1-antitrypsin, a Protease inhibitor (pharmacology), protease inhibitor that belongs to the serine family, by matrix metalloproteinases. It was shown that it could interact with the HIV-1 and stop the virus multiplication. In spite of ...
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Entry Inhibitor
Entry inhibitors, also known as fusion inhibitors, are a class of 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 n ...s 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 HIV#Entry to the cell, binding, fusion and entry of an HIV virion to a human cell. By blocking this step in HIV#Replication cycle, 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 to the cell, HIV entry process. * CD4, a protein receptor found on the surface of helper T c ...
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Fusion Inhibitor
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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HIV-1
The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey, a vulnerable West African primate. HIV-1 viruses can be further divided into groups M, N, O and P. The HIV-1 group M viruses predominate and are responsible for the AIDS pandemic. Group M can be further subdivided into subtypes based on genetic sequence data. Some of the subtypes are known to be more virulent or are resistant to different medications. Likewise, HIV-2 viruses are thought to be less virulent and transmissible than HIV-1 M group viruses, although HIV-2 is also known to cause AIDS. One of the obstacles to treatment of the human immunodeficiency virus (HIV) is its high genetic variability. Major types HIV-1 HIV-1 is the most common and pathogenic strain of the virus. Over 2 million such infections occur annually. Scientists ...
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Methionine
Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical role in the metabolism and health of many species, including humans. It is encoded by the codon AUG. Methionine is also an important part of angiogenesis, the growth of new blood vessels. Supplementation may benefit those suffering from copper poisoning. Overconsumption of methionine, the methyl group donor in DNA methylation, is related to cancer growth in a number of studies. Methionine was first isolated in 1921 by John Howard Mueller. Biochemical details Methionine (abbreviated as Met or M; encoded by the codon AUG) is an α-amino acid that is used in the biosynthesis of proteins. It contains a carboxyl group (which is in the deprotonated −COO− form under biological pH conditions), an amino group (which is in the protonated fo ...
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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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T Helper Cell
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases. Structure and function Th cells contain and release cytokines to aid other immune cells. Cytokines are small protein mediators that alter the behavior of target cells that express receptors for those cytokines. These cells help polarize the immune response depending on the nature of the immunological insult ...
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Retrovirus
A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus ''retro'' (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Although retroviruses have different subfamilies, they have three basic groups: the oncoretroviruses (oncogenic retroviruses), the lentiviruses (slow retroviruses) and the spumaviruses (foamy viruses). The oncoretroviruses are able to cause cancer in some species, the lentiviru ...
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Gp120
Envelope glycoprotein GP120 (or gp120) is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1988. The 120 in its name comes from its molecular weight of 120 kDa. Gp120 is essential for virus entry into cells as it plays a vital role in attachment to specific cell surface receptors. These receptors are DC-SIGN, Heparan Sulfate Proteoglycan and a specific interaction with the CD4 receptor, particularly on helper T-cells. Binding to CD4 induces the start of a cascade of conformational changes in gp120 and gp41 that lead to the fusion of the viral membrane with the host cell membrane. Binding to CD4 is mainly electrostatic although there are van der Waals interactions and hydrogen bonds. Gp120 is coded by the HIV ''env'' gene, which is around 2.5 kb long and codes for around 850 amino acids.Kuiken, C., Leitner, T., Foley, B., ''et al.'' (2008)"HIV Sequence Compe ...
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Glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated. In proteins that have segments extending extracellularly, the extracellular segments are also often glycosylated. Glycoproteins are also often important integral membrane proteins, where they play a role in cell–cell interactions. It is important to distinguish endoplasmic reticulum-based glycosylation of the secretory system from reversible cytosolic-nuclear glycosylation. Glycoproteins of the cytosol and nucleus can be modified through the reversible addition of a single GlcNAc residue that is considered reciprocal to phosphorylation and the functions of these are likely to be an additional regulatory mechanism that controls phosphorylation-based signalling. In contrast, ...
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Host Cell
In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include animals playing host to parasitic worms (e.g. nematodes), cells harbouring pathogenic (disease-causing) viruses, a bean plant hosting mutualistic (helpful) nitrogen-fixing bacteria. More specifically in botany, a host plant supplies food resources to micropredators, which have an evolutionarily stable relationship with their hosts similar to ectoparasitism. The host range is the collection of hosts that an organism can use as a partner. Symbiosis Symbiosis spans a wide variety of possible relationships between organisms, differing in their permanence and their effects on the two parties. If one of the partners in an association is much larger than the other, it is generally known as the host. In parasitism, the parasite benefits at the ...
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