Ganciclover

Ganciclovir, a guanine derivative, is triphosphorylated to form a nucleotide that inhibits DNA polymerases of cytomegalovirus (CMV), and HSV and causes chain termination. The first phosphorylation step is catalyzed by virus-specific enzymes in both CMV-infected and HSV-infected cells. CMV resistance mechanisms involve mutations in the genes that code for the activating viral phosphotransferase and the viral DNA polymerase. Thymidine kinase-deficient HSV strains are resistant to ganciclovir.that has 8 to 20 times greater activity against CMV, which is the only viral infection for which it is approved. It is currently available for treatment of CMV retinitis in immunocompromised patients and for CMV prophylaxis in transplant patients.Like acyclovir, ganciclovir is activated through conversion to the nucleoside triphosphate by viral and cellular enzymes, with the actual pathway depending on the virus. CMV is deficient in thymidine kinase and, therefore, forms the triphosphate by another route. The nucleotide competitively inhibits viral DNA polymerase and can be incorporated into the DNA, thereby decreasing the rateof chain elongation.