Cidofovir does not require activation by viral thymidine kinase; therefore, it would be best suited to treat the thymidine kinase-deficient varicella-zoster virus.
Acyclovir, famciclovir, and ganciclovir are guanosine analogs that are used as viral DNA polymerase inhibitors to treat HSV, VZV, and EBV. The three analogs require phosphorylation for activation. The first step in phosphorylation is monophosphorylation by the HSV/VZV thymidine kinase; further phosphorylation is then performed by the host cells to form the triphosphate. Finally, the drug is incorporated into the viral DNA molecule, terminating replication. Resistance arises when the virus lacks thymidine kinase and these analogs cannot be activated; therefore, cidofovir, which does not require phosphorylation by a viral kinase, must be used.
Stankus et al. review the management of shingles, stating that it is due to the reactivation of the varicella-zoster virus acquired previously. It is typically treated with acyclovir, famciclovir, or valacylcovir. Medications are most effective if taken within 72 hours of the appearance of the rash. Corticosteroids may be useful in reducing the pain associated with shingles and the ensuing postherpetic neuralgia.
De Clercq discusses the mechanism of phosphorylation for cidofovir. It is first phosphorylated by the host pyrimidine nucleoside monophosphate kinase followed by phosphorylation by nucleoside diphosphate, pyruvate kinase, or creatine kinase to create the active form.
Illustration A shows the mechanism of acyclovir resistance; reduced production of viral thymidine kinase leads to decreased generation of acyclovir triphosphate, which results in a failure to inhibit viral DNA polymerase.
Answers 1-3: Acyclovir, famciclovir, and ganciclovir are viral DNA polymerase inhibitors that require activation by viral thymidine kinase.
Answer 5: Amantadine is used to treat influenza A and does so by blocking viral attachment, penetration, or uncoating.
Stankus SJ, Dlugopolski M, Packer D. Management of herpes zoster (shingles) and postherpetic neuralgia. Am Fam Physician. 2000 Apr 15;61(8):2437-44, 2447-8. Review.
PMID:10794584 (Link to Abstract)
De Clercq E. Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections. Clin Microbiol Rev. 2003 Oct;16(4):569-96. Review.
PMID:14557287 (Link to Abstract)