ACYCLOVIR: Mechanisms Prodrug-must be activated ACYCLOVIR (e.g. herpes simplex virus Step 1 thymidine kinase) Viral thymidine kinase Modified acyclovir inhibits synthesis of viral dNa by Monophosphate derivative Step 2 1. Binding irreversibly to viral DNA template Host kinase(s) 2. Termination of dna elongation after incorporation into viral DNA Di-and triphosphate analogs Di-and triphosphates are only accumulated in infected cellsACYCLOVIR: Mechanisms ACYCLOVIR Viral thymidine kinase Monophosphate derivative Host kinase(s) Di- and triphosphate analogs Di- and triphosphates are only accumulated in infected cells • Prodrug – must be activated (e.g. herpes simplex virus thymidine kinase). • Modified Acyclovir inhibits synthesis of viral DNA by: 1. Binding irreversibly to viral DNA template 2. Termination of DNA elongation after incorporation into viral DNA Step 1 Step 2