What is a Maturation Inhibitor?

Maturation is one of the final steps of the HIV life cycle and involves the processing of viral proteins required by HIV in order to become infectious. HIV maturation inhibitors are a potentially promising new class of molecules that are under study for their ability to prevent the processing of these proteins. Researchers are anticipating that the use of a maturation inhibitor will prove effective at preventing the HIV virus from infecting other cells in the body.

In a simplified version of the HIV life cycle, HIV first binds and fuses with the membrane of the target host cell in order to inject the virus’s contents into the cell. The HIV genome is then reverse transcribed, which refers to the conversion from ribonucleic acid (RNA) to deoxyribonucleic acid (DNA), and the viral DNA is integrated into the host cell's genome. At this point, the virus may lie dormant for a period of time, or it may immediately begin to produce viral products such as new viral RNA and proteins, which will be necessary for the subsequent assembly and release of the infectious virion.

The crucial step during the process of HIV maturation involves the processing of the gag protein. Gag is actually a polyprotein, which means that it is originally produced as a long thread of different proteins that will later be cut into functional pieces. The gag protein must be cut into smaller pieces by HIV proteases to produce structural proteins that are crucial for the assembly of an infectious HIV virion. A maturation inhibitor functions by interfering with gag processing by binding to the gag polyprotein and preventing HIV proteases from cutting it, resulting in virus particles incapable of infecting other host cells.

Development of a new class of HIV inhibitors is important because HIV treatment therapies often include a variety of drugs from different classes that are taken together to strike as many phases of the HIV life cycle as possible. In addition, it is well known that HIV is able to mutate during drug exposure, resulting in drug resistance, and producing HIV strains resistant to entire classes of drugs. The introduction of a new drug such as a maturation inhibitor, therefore, presents a new class of inhibitor from which an effective treatment regime may be established for people who have exhausted all their drug options. Bevirimat, a maturation inhibitor that was first isolated from a Chinese herb, has shown promising results in clinical trials.