Browsing Pathways

Zalcitabine is a dideoxynucleoside used to treat HIV. 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. Zalcitabine (dideoxycytidine) enters the cell and is converted into dideoxycytidine monophosphate by deoxycytidine kinase. UMP-CMP kinase then converts dideoxycytidine monophosphate into dideoxycytidine diphosphate. Dideoxycytidine diphosphate is metabolized to dideoxycytidine triphosphate via nucleoside diphosphate kinase. Dideoxycytidine triphosphate is an analog of deoxycytidine-5'-triphosphate (dCTP). Dideoxycytidine triphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with its substrate, dCTP and by incorporation into viral DNA. Dideoxycytidine triphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once dideoxycytidine 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.

Zalcitabine (ddc) is a dideoxynucleoside antiretroviral drug that when used in combination with zidovudine improves the viral load and CD4+ cell count of patients infected with Human Immunodeficiency Virus Type 1 (HIV-1). Zalcitabine is phosphorylated to it’s active form metabolite 2′,3′-dideoxycytidine 5′-triphosphate (ddCTP) in both healthy and infected cells. ddCTP competes with deoxycytidine triphosphate inhibiting the enzyme reverse transcriptase from using the substrates to elongate the viral DNA strand ultimately halting HIV replication.

Metabolites of sildenafil are predicted with biotransformer.

Metabolites of Yohimbine are predicted with biotransformer.