Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Reverse transcriptase inhibitors are an important part of HAART, or highly active antiretroviral therapy, which is the combination of medications used in the treatment of AIDS.

AIDS is caused by a RNA containing retrovirus called human immunodeficiency virus, or HIV. The “retro” part of retrovirus isn’t referring to its style, but refers to it needing to use an enzyme called reverse transcriptase to transcribe a piece of “proviral” DNA from its RNA.

As the name suggests, reverse transcriptase inhibitors go and inhibit this enzyme, and prevent HIV replication.

They can either be nucleoside reverse transcriptase inhibitors, or NRTIs, which resemble nucleosides, which are the building blocks of nucleic acids like DNA and RNA; or non-nucleoside reverse transcriptase inhibitors, or NNRTIs, which dont resemble nucleosides.

HIV is a single-stranded, positive-sense, enveloped RNA retrovirus that targets cells in the immune system that have a molecule called CD4 on their membrane.

These include macrophages, dendritic cells, and especially CD4+ T-helper cells. Normally, the CD4 molecule helps these cells attach to and communicate with other immune cells, which is particularly important when the cells are launching attacks against foreign pathogens.

HIV attaches to the CD4 molecule via a protein called gp120 found on its envelope. Now, inside its envelope, HIV contains a nucleocapsid which is a capsule containing a single-stranded RNA and some viral enzymes, like reverse transcriptase and integrase.

As HIV bind to the receptors, the viral envelope fuses with the cell membrane of the immune cell, releasing the contents of the nucleocapsid into the helpless host cell’s cytoplasm.

Once it’s inside the CD4+ cell, reverse transcriptase gets to work immediately. It uses the single stranded viral RNA as a template, and uses the nucleotides present in the cytoplasm of the CD4+ cell to transcribe a complementary double-stranded “proviral” DNA.

Proviral just means that it’s ready to be integrated into the host’s DNA, so it enters the T-helper cell’s nucleus and pops itself into the cell’s DNA, ready to be transcribed into new viruses, pretty sneaky, huh?