Nucleotide Analogs: Cidofovir
In recent years a new series of antiviral compounds, the nucleotide analogs, have been developed. The best known example of this class of compounds is cidofovir. This com-pound mimics a monophosphorylated nucleotide by having a phosphonate group attached to the molecule. This appears to the cell as a nucleoside monophosphate, or nucleotide, and cellular enzymes then add two phosphate groups to generate the active compound. In this form, the drug inhibits both viral and cellular nucleic acid polymerases but selectivity is provided by its higher affinity for the viral enzyme.
Nucleotide analogs do not require phosphorylation, or activation, by a viral-encoded enzyme and remain active against viruses that are resistant due to mutations in codons for these enzymes. Resistance can develop with mutations in the viral DNA polymerase, UL54. An additional feature of cidofovir is a very prolonged half-life, due to slow clear-ance by the kidneys.
Cidofovir is approved for intravenous therapy of CMV retinitis, and maintenance treatment may be given as infrequently as every 2 weeks. Nephrotoxicity is a serious complication of cidofovir treatment, and patients must be monitored carefully for evi-dence of renal impairment.
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