<unk>  is a prodrug for ganciclovir, which is a synthetic analog of 2′-deoxy-guanosine. Its structure is the same as ganciclovir, except for the addition of a L-valyl ester at the 5' end of the incomplete deoxyribose ring. The valine increases both the absorption of the drug in the intestines, as well as the bioavailability of the drug once it is absorbed. The L-valyl ester is cleaved by esterases in the intestines and the liver, leaving ganciclovir to be absorbed by the virus-infected cells. Ganciclovir is first phosphorylated to ganciclovir monophosphate by a viral thymidine kinase encoded by the cytomegalovirus (CMV) upon infection. Human cellular kinases further phosphorylate the molecule to create ganciclovir diphosphate, then ganciclovir triphosphate. These kinases are present in 10-fold greater concentrations in CMV or herpes simplex virus (HSV)-infected cells compared to uninfected human cells, allowing ganciclovir triphosphate to concentrate in infected cells. Ganciclovir triphosphate is a competitive inhibitor of deoxyguanosine triphosphate (dGTP). It is incorporated into viral DNA and preferentially inhibits viral DNA polymerases more than cellular DNA polymerases. Ganciclovir triphosphate serves as a poor substrate for chain elongation. Once incorporated into viral DNA due to its structure similarity to dGTP, chain termination occurs once a single nucleotide is added to the distal hydroxyl group of the incomplete deoxyribose ring of ganciclovir.
Valganciclovir
Ganciclovir
Aciclovir
Penciclovir
Famciclovir
Letermovir
Cidofovir
Valaciclovir