Category: catabolism
Nucleoside/nucleotide analogs are activated by stepwise phosphorylation (host or viral kinase) → triphosphate → incorporated by viral polymerase → chain termination (no 3'-OH) or fatal mutagenesis. Acyclovir family is selectively phosphorylated by HSV/VZV thymidine kinase (not host kinase) → herpes-specific. Tenofovir is acyclic nucleotide (already monophosphate) → fewer activation steps → HIV/HBV. NRTIs (zidovudine, abacavir, lamivudine, emtricitabine, etc.) terminate HIV RT. Sofosbuvir terminates HCV NS5B. Remdesivir + molnupiravir target the SARS-CoV-2 RdRp (different mechanisms — chain termination vs lethal mutagenesis). Entecavir terminates HBV polymerase. Ganciclovir is the CMV-active acyclovir analog (UL97 phosphorylation step).