Maraviroc HIV Drug

Maraviroc is a drug used in the treatment of HIV infection.Maraviroc is an entry inhibitor. Specifically, maraviroc blocks the chemokine receptor CCR5 which HIV uses as a co receptor to bind and enter a human helper T cell. Because HIV can also use another co receptor, CXCR4, an HIV tropism test such as a trofile assay must be performed to determine if the drug will be effective.



The first step in HIV1 life cycle is viral attachment to the CD4 T-cell surface, the next step is viral entry which involves a cascade of molecular interactions between the viral envelope glycoprotein and two T-cell surface receptors, a primary receptor and a co-receptor. The GP 120 subunit of the envelope protein first binds the CD4 primary receptor this induces a conformational change in GP 120 that allows the co-receptor binding this Binding triggers conformational changes in the GP 41 subunit leading to insertion of its N-terminal fusion peptide into the host cell's membrane.Fusion results release of the viral genome into the cytoplasm .the co-receptors are the members of the superfamily of G-protein coupled receptors over more than a dozen types of co-receptors have been described .But only two co-receptors such as areas of the CCR5 and CXCR4 are used by all HIV-1 strains.
The co-receptors play a crucial role in HIV disease became evident when the common mutational variant of the CCR5 coding gene known as Delta 32 was discovered in 1996 This CCR5 genetic variant results in the production of nonfunctional CCR5 co receptors .The persons with two normal copies of the CCR5gene predominates in the population and are susceptible to HIV infection.The persons who inherit two copies of the CCR5 delta 32 variant from their parents known as delta 32 homozygotes of non functional CCR5 co receptors are appear to be highly resistant to HIV infection.Delta 32 homozygotes that appears not to be associated with any significant deleterious effects. Delta 32 heterozygotes inherit one copy of the CCR5 delta 32 variant from one parent in the normal form of the CCR5gene from the other parent, Delta 32 heterozygotes can become infected with HIV disease progression is significantly delayed compared to those who have two normal copies of the CCR5 gene. To be effective the co receptor antagonist must be directed at a specific co-receptor CCR5 ,THE co-receptor antagonist for example functions by binding specifically to the CCR5 co receptor molecule, The bound co-receptor is blocked from binding the viral GP 120 subunit which prevents the conformational changes on GP 41 which prevents viral particle entry and HIV particles are unable to enter the T cell cannot infected and cannot replicate. Different HIV strains vary in their ability to use the major co-receptors to achieve entry into the host cell some HIV strains easily use CCR5 co receptor summoning the CX Cr4 for a receptor while other viruses geotropic use both. In HIV-infected individual may have only the CCR5 using virus or the CXCR4 using virus or a mixture of CCR5 using CXCR4 using duo tropic viruses.In the early phase of infection the CCR5 using virus predominates in most patients in the late phase of infection HIV strains capable of using CXCR4 recptoe. Unlike reverse transcripase or protease inhibitors which went inside the infected cell to receptor ,Antagonists function on the outside of the host cell,The co-receptor antagonists are therefore classified as entry inhibitors. the mechanism of action of co-receptor antagonists differs from other antiretroviral in a very important way rather than binding to viral proteins this new class prevents viral replication by binding to human cells such as T cells and macrophages this unique mechanism has potential clinical advantages.

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