What Are Nonnucleoside Reverse Transcriptase Inhibitors?

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  • Written By: Jillian O Keeffe
  • Edited By: Shereen Skola
  • Last Modified Date: 20 October 2019
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Nonnucleoside reverse transcriptase inhibitors (NNRTI) are a group of antiviral medications. They target an enzyme that the human immunodefiency virus (HIV) uses to replicate inside host cells. Although the drugs are not a cure for HIV infection, they act as part of a treatment regimen that can help control the progress of disease.

Reverse transcriptase is an enzyme that several viral pathogens use to replicate in hosts. The NNRTI drugs inhibit the enzyme, and stop it from doing its job. The nonnucleoside portion of the name refers to the particular way this drug group acts on the enzyme. Even though various viruses use a reverse transcriptase enzyme, doctors generally only use the term nonnucleoside reverse transcriptase inhibitors for HIV drugs.

A HIV viral particle is small, and doesn't contain all the genetic material, or structural machinery, to replicate itself. It does, however, carry specific genes that code for products it can use to hijack a host cell's existing machinery. Reverse transcriptase is one of these viral products.

Human cells use deoxyribonucleic acid (DNA) as genetic material. HIV uses ribonucleic acid (RNA). This poses a problem for the virus, because it needs to work with the cell machinery, which is controlled through DNA, to make new RNA viruses. The reverse transcriptase enzyme acts as the go-between. It reads the RNA of the virus and creates a DNA version for the cell to read. The cell then recognizes the DNA instructions, and produces RNA viral particles.


Research scientists identified this enzyme as a essential step in HIV replication, and therefore a target for potential drugs. An enzyme is basically a molecule that has a specific structure, and that recognizes, and binds to, other biological molecules. The site where the molecules bind is called the active site.

Some drugs bind directly to the active site of an enzyme, and block the enzyme from interacting with its target molecules, because the targets cannot fit into the active site. Nonnucleoside reverse transcriptase inhibitors actually bind to a different part of the enzyme, but still block the molecules that the enzyme is supposed to interact with. This, in theory, slows down the replication process of the HIV particle.

Problems exist in HIV treatment where the virus can mutate. RNA mutates relatively easily, as the copying mechanisms from one RNA particle to another are not always exact. When the HIV virus mutates during replication, the reverse transcriptase enzyme can be slightly different, and so be less recognizable to the nonnucleoside reverse transcriptase inhibitors. This can be detrimental to the success of the drugs.

Due to this resistance mechanism of HIV, patients typically receive nonnucleoside reverse transcriptase inhibitors as part of a treatment regimen along with other forms of antiviral medication. The NNRTIs form a group of medicines based on their actions on the enzyme, but can have different structures. Examples of NNRTIs include nevirapine, rilpivirine and efavirenz.


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