Maturation inhibitor

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Maturation inhibitors are drugs from the group of virustatic agents .

history

Research into maturation inhibitors has been going on for a long time. However, it wasn't until 2005 that the decisive breakthrough came in the development of this class of active ingredients.

effect

Maturation inhibitors intervene at a late stage in virus replication and prevent the assembly of new virus particles from the viral building blocks within the cell. A virus precursor protein is broken down into different functional and structural proteins by the virus protease. The maturation inhibitors bind to the precursor protein (e.g. CA-SP1) and inhibit the cleavage by the HIV protease. As a result, no functional virus protein envelope can be built up.

Side effects

First clinical studies on active ingredients in this substance class have shown good tolerability. Please also read the instructions for the individual active ingredients.

application areas

Maturation inhibitors are used to combat viruses. Active substances against HIV currently exist .

HIV therapy

Maturation inhibitors are an interesting new class of substances in the context of HAART . However, they first have to pass phase IIb / phase III studies. It remains unclear whether drugs like Bevirimat will make it into the clinic. The first studies of proven effectiveness give new hope. It is therefore clear that HIV can also be attacked from a new angle in the clinic.

Active ingredients

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  1. ↑ Martin D, Jacobson J, Schurmann D, et al. PA-457, the first-in-class maturation inhibitor, exhibits antiviral activity following a single oral dose in HIV-1 infected patients. Abstract 159, 12th CROI 2005, Boston.
  2. ↑ Active ingredient BMS-955176 from Bristol-Myers Squibb, currently in clinical phase 2

literature

  • Li F, Goila-Gaur R, Salzwedel K, et al. (2003): PA-457: a potent HIV inhibitor that disrupts core condensation by targeting a late step in gag processing. In: Proc. Natl. Acad. Sci. USA 100, 13555-13560. PMID 14573704
  • Adamson C, Salzwedel K, Castillo A, et al. Viral resistance to PA-457, a novel inhibitor of HIV-1 maturation. Abs. 156, 13th CROI 2006, Denver.
  • Beatty G, Jacobson J, Lalezari J, et al. Safety and Antiviral Activity of PA-457, the First-In-Class Maturation Inhibitor, in a 10-Day Monotherapy Study in HIV-1 Infected Patients. Abstract H-416D, 45th ICAAC 2005, Washington.
  • Blair W, Cao J, Jackson L, et al. Execution of a high throughput HIV-1 replication screen and the identification of a novel small molecule inhibitor that targets HIV-1 envelop maturation. Abstract 50LB, 13th CROI 2006, Denver.
  • Kilgore N, Reddick M, Zuiderhof M, et al. The first-in-class maturation inhibitor, PA-457, is a potent inhibitor of HIV-1 drug-resistant isolates and acts synergistically with approved HIV drugs in vitro. Abstract 509, 13th CROI 2006, Denver.
  • Martin D, and others. The safety, tolerability, and pharmacokinetics of multiple oral doses of PA-457, the first-in-class HIV maturation inhibitor, in healthy volunteers. Abstract 551th 12th CROI 2005, Boston.
  • Martin D, Jacobson J, Schurmann D, et al. PA-457, the first-in-class maturation inhibitor, exhibits antiviral activity following a single oral dose in HIV-1 infected patients. Abstract 159, 12th CROI 2005, Boston.
  • Smith P, Forrest A, Beatty G, et al. Pharmacokinetics / pharmacodynamics of PA-457 in a 10-day multiple dose monotherapy trial in HIV-infected patients. Abstract 52, 13th CROI 2006, Denver.