CH 2 OCH 2 CH 2 ONNOH 2 N NHNAcyclovirO
CH 3OHNNHOON 3
Zidovudine (AZT) VidarabineHO HOHONH 2ONN NNFigure 7.16 Examples of viral nucleic acid synthesis inhibitors that form triphosphate drug
derivativesin situ
cell’s cellular kinases. This conversion may also involve specific viral enzymes in
the initial monophosphorylation step. These triphosphate drug derivatives are
incorporated into the nucleic acid chain, where they terminate its formation.
Termination occurs because the drug residues do not have a 3’hydroxy group
necessary for the phosphate ester formation, required for further growth of the
nucleic acid chain. This effectively inhibits the polymerases and transcriptases
that catalyse the growth of the nucleic acid. In addition, these drugs also inhibit
other enzymes involved in the nucleic acid chain formation.
7.6.2 Host cell penetration inhibitors
The principal drugs that act in this manner are amantadine and rimantadine
(Figure 7.17). Amantadine hydrochloride is effective against influenza A virus
but is not effective against the influenza B virus. It is believed to acts by blocking
an ion channel in the virus membrane formed by the viral protein M 2. This is
believed to inhibit the disassembly of the core of the virion and its penetration of
the host. However, its use can result in depression, dizziness, insomnia and
gastrointestinal disturbances amongst other unwanted side effects. Rimantadine
hydrochloride is an analogue of amantadine hydrochloride that exhibits signifi-
cantly fewer CNS side effects.
CH 3 NH 3 Cl−+
NH 3 Cl−+Amantadine hydrochloride Rimantadine hydrochlorideFigure 7.17 Examples of host cell penetration inhibitors156 SELECTED EXAMPLES OF DRUG ACTION AT SOME COMMON TARGET AREAS