Anti-herpes medications disrupt the process by which the virus makes copies of itself and spreads to new cells. They work by inhibiting an enzyme that the virus has but human cells do not have and then interrupting the viruses' ability to synthesize DNA.
Nucleoside analogues are highly potent and selective inhibitors of viral enzyme thymidine kinase (TK). They depend on the activity of the viral thymidine kinase to convert the drug to a monophosphate form and subsequently interfere with viral DNA replication.
The principle of antiviral activity of nucleoside analogues acyclovir and penciclovir relies on the fact that herpes viruses (herpes simplex virus, varicella zoster virus and cytomegalovirus) encode their own nucleoside kinases which have a much lower substrate specificity than their cellular counterparts. Therefore, they are able to monophosphorylate certain nucleoside analogues whereas cellular nucleoside kinases cannot do so or only to a very limited extent.
The resulting analogue monophosphates are metabolized, by cellular kinases, to the respective triphosphates, which show distinctly lower molar inhibitory constants (Ki values) for herpes virus-encoded DNA polymerases than for cellular DNA polymerases. This step of antiviral selectivity causes obligate chain termination in the case of acyclovir and, thus, cessation of virus production. On the other hand, in contrast to acyclovir, which has only one hydroxyl group in its acyclic "sugar" moiety, penciclovir possess two hydroxyl groups and can be internally incorporated into the growing DNA chain. Its mode of antiviral action is less well understood so far.