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Maturation Inhibitor
The maturation inhibitors are a class of antiviral drugs for the treatment of infection with HIV. They act by interfering with the maturation of the virus. Specifically, drugs in this class disrupt the final step in the processing of the HIV-1 ''gag'' protein, the cleavage of its immediate precursor by the enzyme HIV-1 protease. Unlike the class of drugs known as protease inhibitors, maturation inhibitors bind the ''gag'' protein, not the protease. This leads to the formation of noninfectious, immature virus particles, incapable of infecting other cells. No other class of drugs shares this mechanism of action, thus maturation inhibitors retain inhibitory activity against HIV infections with resistance. There are no currently available drugs from the class; however several clinical trials have been conducted. The first maturation inhibitor to be studied in humans was bevirimat, another was MPC-9055 (vivecon). Both were developed by Myriad Genetics Myriad Genetics, Inc. is an ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Group-specific Antigen
Group-specific antigen, or gag, is the polyprotein that contains the core structural proteins of an Ortervirus (except ''Caulimoviridae''). It was named as such because scientists used to believe it was antigenic. Now it is known that it makes up the inner shell, not the envelope exposed outside. It makes up all the structural units of viral conformation and provides supportive framework for mature virion. All orthoretroviral ''gag'' proteins are processed by the protease (PR or ''pro'') into MA (matrix), CA (capsid), NC (nucleocapsid) parts, and sometimes more. If Gag fails to cleave into its subunits, virion fails to mature and remains uninfective. It comprises part of the ''gag-onc'' fusion protein. Gag in HIV Numbering system By convention, the HIV genome is numbered according to HIV-1 group M subtype B reference strain HXB2. Transcription and mRNA processing After a virus enters a target cell, the viral genome is integrated into the host cell chromatin. RNA polymer ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HIV-1 Protease
HIV-1 protease (PR) is a retroviral aspartyl protease (retropepsin), an enzyme involved with peptide bond hydrolysis in retroviruses, that is essential for the life-cycle of HIV, the retrovirus that causes AIDS. HIV protease cleaves newly synthesized polyproteins (namely, Gag and Gag- Pol) at nine cleavage sites to create the mature protein components of an HIV virion, the infectious form of a virus outside of the host cell. Without effective HIV protease, HIV virions remain uninfectious. Structure Mature HIV protease exists as a 22 kDa homodimer, with each subunit made up of 99 amino acids. A single active site lies between the identical subunits and has the characteristic Asp- Thr- Gly (Asp25, Thr26 and Gly27) catalytic triad sequence common to aspartic proteases. As HIV-1 PR can only function as a dimer, the mature protease contains two Asp25 amino acids, one from each monomer, that act in conjunction with each other as the catalytic residues. Additionally, HIV protea ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protease Inhibitor (pharmacology)
Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS and hepatitis C. These protease inhibitors prevent viral replication by selectively binding to viral proteases (e.g. HIV-1 protease) and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles. Protease inhibitors that have been developed and are currently used in clinical practice include: * Antiretroviral HIV-1 protease inhibitors—class stem ** Amprenavir ** Atazanavir ** Darunavir ** Fosamprenavir ** Indinavir ** Lopinavir ** Nelfinavir ** Ritonavir ** Saquinavir ** Tipranavir * Hepatitis C virus NS3/ 4A protease inhibitors—class stem ** Asunaprevir ** Boceprevir ** Grazoprevir ** Glecaprevir ** Paritaprevir ** Simeprevir ** Telaprevir * Severe acute respiratory syndrome coronavirus 2 3-chymotrypsin-like protease inhibitors ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bevirimat
Bevirimat (research code MPC-4326) is an anti-HIV drug derived from a betulinic acid-like compound, first isolated from ''Syzygium claviflorum,'' a Chinese herb. It is believed to inhibit HIV by a novel mechanism, so-called maturation inhibition. It is not currently U.S. Food and Drug Administration (FDA) approved. It was originally developed by the pharmaceutical company Panacos and reached Phase IIb clinical trials. Myriad Genetics announced on January 21, 2009 the acquisition of all rights to bevirimat for $7M USD. On June 8, 2010 Myriad Genetics announced that it was halting the development of maturation inhibitors, including bevirimat, to focus more on their oncology portfolio. Pharmacokinetics According to the only currently available study, "the mean terminal elimination half-life of bevirimat ranged from 56.3 to 69.5 hours, and the mean clearance ranged from 173.9 to 185.8 mL/hour." Mechanism of action Like protease inhibitors, bevirimat and other maturation inhibito ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Myriad Genetics
Myriad Genetics, Inc. is an American genetic testing and precision medicine company based in Salt Lake City, Utah, United States. Myriad employs a number of proprietary technologies that permit doctors and patients to understand the genetic basis of human disease and the role that genes play in the onset, progression and treatment of disease. This information is used to guide the development of new products that assess an individual's risk for developing disease later in life (predictive medicine), identify a patient's likelihood of responding to a particular drug therapy (precision medicine), assess a patient's risk of disease progression and disease recurrence (precision medicine), and measure disease activity. History The global search for the genetic basis of breast cancer began in April 1978 when Dr. Mark Skolnick began his research on family disease and linkages at the University of Utah. Numerous other groups also worked to locate BRCA, including Mary-Claire King, Ph.D., ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BMS-955176
BMS-955176 is an experimental second generation HIV maturation inhibitor under development by Bristol-Myers Squibb for use in the treatment of HIV infection. By blocking the maturation of the virus, it prevents viral reproduction in host CD4+ T cells. First generation maturation inhibitors such as bevirimat were ineffective against some naturally occurring changes (polymorphisms) in the Gag protease polyprotein; BMS-955176 has been selected to better tolerate gag polymorphisms. __TOC__ Studies Results of a phase 2a trial of BMS-955176 was reported at the 2015 Conference on Retroviruses and Opportunistic Infections The Conference on Retroviruses and Opportunistic Infections (CROI) is an annual scientific meeting devoted to the understanding, prevention and treatment of HIV/AIDS and the opportunistic infection An opportunistic infection is an infection ca ... (CROI). Investigators concluded that the drug was well tolerated and effective against HIV, including strains with ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fipravirimat
Fipravirimat is an experimental drug for the treatment of HIV/AIDS. It belongs to a class of drugs known as maturation inhibitors. Fipravirimat is being developed by ViiV Healthcare and as of 2023 is in Phase II clinical trials. See also * BMS-955176 BMS-955176 is an experimental second generation HIV maturation inhibitor under development by Bristol-Myers Squibb for use in the treatment of HIV infection. By blocking the maturation of the virus, it prevents viral reproduction in host CD4+ T ... References {{antiinfective-drug-stub Antiviral drugs Carboxylic acids Organofluorides Pentacyclic compounds Sulfones ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
