Antiviral Nucleoside Inhibitors

Antiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis.

For example, acyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus types 1 and 2, and varicella-zoster virus.

Acyclovir enters the infected cell through passive diffusion. In the cytoplasm, virus-encoded thymidine kinase phosphorylates acyclovir to form acyclovir monophosphate.

Then, host kinases convert acyclovir monophosphate step by step into its diphosphate and active triphosphate forms.

Acyclovir triphosphate enters the nucleus, where it mimics deoxyguanosine triphosphate and is mistakenly incorporated by viral DNA polymerase into the growing viral DNA strand.

Acyclovir triphosphate lacks a 3′-hydroxyl group, so it blocks further addition of nucleotides to the DNA strand.

This prematurely terminates DNA synthesis. As a result, viral replication is halted.