Protease inhibitors (PIs) play an important role in highly active antiretroviral therapy (HAART)1,2.
HIV researchers realised early on that if they can prevent virions from reaching maturity, they may slow down the virus’ ability to replicate. This finding ultimately led to the development of the first PI.
Protease is an enzyme in the body that’s important for HIV replication
Viruses are often referred to as the ‘perfect’ parasite. A virus cannot reproduce on its own, so in order to make new copies, it must infect host cells of the immune system (CD4 cells)3.
As a new virion (an individual virus) buds out from an infected host cell, it is wrapped by the cell’s bilayer membrane and carries with it any protein that happens to be embedded in the membrane at the budding site. Enveloped viruses such as HIV are then free to begin a new cycle of infection by fusing their cell-derived envelope with the cellular membrane of an uninfected cell.
A virion’s machinery is so efficient that each cell infected by even a single virion can produce about a million new virions3.
However, before it can become infectious, virions have to undergo certain morphological structural changes. This is where protease enzymes come into play.
The virus uses these enzymes to break down polyproteins into smaller units needed to mature and assemble new viral particles2.
HIV researchers realised early on that if they can prevent virions from reaching maturity, they may slow down the virus’ ability to replicate. This finding ultimately led to the development of the first PI1,4,5.
The first PI (ritonavir [RTV or /r]) was approved by the American Food and Drug Administration (FDA) in 1996. Since then, 10 more PIs have been approved by the FDA, making them the largest class of drugs used in the fight against HIV1,4,5.