Which antiviral agent needs to be activated by cellular phosphorylation?

Acyclovir is the correct answer because it is a nucleoside analog that requires phosphorylation within host cells to be converted into its active form, acyclovir triphosphate. The activation process involves a series of phosphorylation steps, where the drug is first phosphorylated by viral thymidine kinase and then further phosphorylated by cellular kinases. The active triphosphate form inhibits viral DNA polymerase and incorporates itself into viral DNA, leading to chain termination during viral replication.

In contrast, Oseltamivir, which is a neuraminidase inhibitor, does not require any cellular activation for its antiviral activity. Instead, it works by preventing the release of new viral particles from infected cells. Zidovudine, an antiretroviral drug, also does not need cellular phosphorylation in the same way as acyclovir, as it can be phosphorylated through different pathways. Valacyclovir is a prodrug of acyclovir and is converted into acyclovir in the body, but it still relies on acyclovir's necessity for phosphorylation to become active.