Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) used in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV) infections. When HIV infects a cell, the virus first binds and fuses with the cell, releasing its nucleocapsid containing its RNA and reverse transcriptase into the cytosol of the cell. The reverse transcriptase converts the viral RNA into viral DNA in the cytosol. The viral DNA goes to the nucleus through the nuclear pore complex where it undergoes the process of transcription. The new viral RNA formed from transcription is transported back to the cytosol through the nuclear pore complex and translation occurs to produce viral proteins. These viral proteins are assembled and new HIV viruses bud from the cell. Zidovudine enters the cell via solute carrier family 22 member 6 and is converted into zidovudine monophosphate by thymidine kinase. Thymidylate kinase then converts zidovudine monophosphate into zidovudine diphosphate. Zidovudine diphosphate is metabolized to zidovudine triphosphate via nucleoside diphosphate kinase A. Zidovudine triphosphate is an analog of deoxyguanosine triphosphate (dGTP). Zidovudine diphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with its substrate, dGTP and by incorporation into viral DNA. Zidovudine triphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once Zidovudine triphosphate gets incorporated into DNA, this causes DNA chain termination, preventing the growth of viral DNA. Less viral proteins are therefore produced, and there is a reduction in new viruses being formed. Zidovudine has a high frequency of side effects that limits its use. Side effects of taking zidovudine may include nausea, vomiting, diarrhea, headaches, myalgia, insomnia, bone marrow suppression, peripheral myopathy, elevated liver enzyme, lactic acidosis and hepatotoxicity.

Zidovudine Anti-Viral Pathway References