What Is a Protease Inhibitor?

To best explain what a protease inhibitor is, let's start with a basic review of the biology of viruses, such as HIV. Firstly, HIV is a virus that attacks the immune system by infecting cells of the immune system. The infection does not kill the cell immediately, but HIV forces the infected cell to make more copies of itself. Copies leave the infected cell and travel to other healthy immune cells, leaving the original host cell to die. This is how HIV destroys the immune system.

The several steps HIV must take to infect a cell and make copies of itself are targets of anti-HIV therapies, which aim to stop viral replication and spread. Protease inhibitors are drugs used to stop HIV protease from working.

How Protease Inhibitors Work

HIV forces infected host cells make copies of the virus. A last step in this process is the creation of new viral proteins. This is the step that is blocked using protease inhibitors.

protease inhibitors

Protease enzymes are not from human cells and are strictly viral proteins. Proteins are all made the same way - through the central dogma of biology: DNA genetic code is copied into RNA form, which serves as an instruction manuals for ribosomes to follow as they create the proteins and polypeptide chains. Viruses do not have this machinery. HIV relies on its host cell, which has theses components, to make copies of HIV proteins. Though copies of HIV proteins are made the same way with the same host machinery, there is a big difference that protease inhibitors can exploit.

While all mammals copy one gene at a time, HIV genes are copied all at once into a single polypeptide chain. The viral proteins are made end-to-end creating a polypeptide. Cell machinery always read the gene copy from beginning to end without stopping. The end-to-end polypeptide must be cut into pieces for the virus to be able to infect other cells. HIV protease is the protein that cuts apart the HIV proteins, and they can be stopped with protease inhibitors.

Protease Inhibitors vs Viruses

Protease inhibitors mimic the link between two viral proteins, but cannot be cut by protease, which is a key characteristic in using it as a tool against viral replication. When an enzyme binds to substrates, it changes it in some way. A protease enzyme binds a polypeptide and cuts it into individual proteins. Until a reaction is complete in the substrate, an enzyme won't release it. The unslicable inhibitor then gets stuck and when all proteases in a cell are inhibited, HIV replication halts in the infected cell.

This production halt in all HIV-infected cells can prevent further spreading, essentially, stopping this and potentially other viral diseases. These antiviral drugs are widely used to treat HIV and hepatitis (C) and have potential in treating cancers. It was found that nelfinavir and atazanavir were able to kill tumor cells in a Petri dish, but the effect was not examined in humans. There are some studies that shown nelfinavir was able to suppress tumor growth in animals, which is a promising lead towards applying it in human clinical studies.

It is the hope that there will be continued research on protease inhibitors as effective treatments against these viral diseases, as well as other pathogenic ones.

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