Nucleoside reverse transcriptase inhibitor

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) are a class of antiretroviral drugs used to treat HIV/AIDS and hepatitis B. They work by inhibiting the action of reverse transcriptase, an enzyme crucial to the replication of these viruses.

Mechanism of Action

NRTIs are prodrugs that become active after being phosphorylated into their triphosphate form within the cell. They mimic the natural substrates of the reverse transcriptase enzyme, which incorporates them into the growing viral DNA chain. However, unlike the natural substrates, NRTIs lack a 3'-hydroxyl group on the deoxyribose sugar. This prevents the addition of further nucleotides, effectively terminating the DNA chain and halting viral replication.

Types of NRTIs

There are several types of NRTIs, including:

• Zidovudine (AZT)
• Didanosine (ddI)
• Zalcitabine (ddC)
• Stavudine (d4T)
• Lamivudine (3TC)
• Abacavir (ABC)
• Emtricitabine (FTC)
• Tenofovir disoproxil (TDF)
• Tenofovir alafenamide (TAF)

Each of these drugs has a unique profile in terms of efficacy, side effects, and resistance patterns.

Side Effects and Resistance

Common side effects of NRTIs include nausea, vomiting, diarrhea, and fatigue. Long-term use can lead to more serious complications such as lactic acidosis, lipodystrophy, and peripheral neuropathy.

Resistance to NRTIs can develop through mutations in the reverse transcriptase enzyme that reduce the drug's binding affinity or increase its excision from the DNA chain. This is a major challenge in the treatment of HIV/AIDS and hepatitis B, necessitating the use of combination therapy and regular monitoring of viral load and resistance mutations.

See Also

• Non-nucleoside reverse transcriptase inhibitors
• Protease inhibitors
• Integrase inhibitors
• Antiretroviral therapy