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.[1][2][3][4]
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,[5] another was MPC-9055 (vivecon).[6] Both were developed by Myriad Genetics, which has discontinued the maturation inhibitor program in 2010.[7] Others in development include BMS-2838232.
References
- ^ Salzwedel K, Martin DE, Sakalian M (2007). "Maturation inhibitors: a new therapeutic class targets the virus structure". AIDS Rev. 9 (3): 162–72. PMID 17982941. Archived from the original on 2016-08-03. Retrieved 2009-02-21.
- ^ Adamson CS, Salzwedel K, Freed EO (August 2009). "Virus maturation as a new HIV-1 therapeutic target". Expert Opin. Ther. Targets. 13 (8): 895–908. doi:10.1517/14728220903039714. PMC 2737327. PMID 19534569.
- ^ Waheed AA, Freed EO (January 2012). "HIV type 1 gag as a target for antiviral therapy". AIDS Res. Hum. Retroviruses. 28 (1): 54–75. doi:10.1089/AID.2011.0230. PMC 3251841. PMID 21848364.
- ^ Jiang Y, Liu X, de Clercq E (2011). "New therapeutic approaches targeted at the late stages of the HIV-1 replication cycle". Curr. Med. Chem. 18 (1): 16–28. doi:10.2174/092986711793979751. PMID 21110817.
- ^ Stoddart CA, Joshi P, Sloan B, Bare JC, Smith PC, Allaway GP, Wild CT, Martin DE (2007). "Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice". PLOS ONE. 2 (11): e1251. Bibcode:2007PLoSO...2.1251S. doi:10.1371/journal.pone.0001251. PMC 2080775. PMID 18043758.
- ^ "New HIV maturation inhibitor MPC-9055". National AIDS Treatment Advocacy Project. 17 September 2008. Retrieved 10 June 2012.
- ^ "Myriad Genetics suspends its HIV Maturation Inhibitor Program". AIDSmeds. 8 June 2012. Archived from the original on 8 September 2015. Retrieved 27 June 2012.