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Cidofovir and Foscarnet

*Cidofovirum*, *Foscarnetum*

For medical students2 min readUpdated 2026-10-10

Cidofovir and Foscarnet are potent antiviral agents that selectively inhibit viral DNA synthesis. These drugs are primarily used in severe cytomegalovirus (CMV) infections.

Chemical natureCidofovir is a nucleotide analogue of cytidine containing a phosphonate group.
Activation mechanismCidofovir is activated exclusively by cellular kinases.
Target siteViral DNA polymerase and reverse transcriptase.
Route of administrationFoscarnet has low oral bioavailability and is administered intravenously.

Cidofovir: Structure and Activation

Structurally, Cidofovirum is a cytidine nucleotide analogue that already possesses a phosphonate group. Its key characteristic is that its metabolism and conversion into the active form (cidofovir diphosphate) are entirely independent of viral enzymes. Activation is carried out exclusively by cellular kinases in both infected and uninfected host cells. Due to this property, the drug successfully overcomes resistance associated with UL97 kinase mutations.

Molecular Mechanism of Action of Cidofovir

The therapeutic effect of cidofovir diphosphate is realized through two main steps:

  1. Competitive inhibition: The active form of the drug competes with natural deoxycytidine triphosphate for binding to viral DNA polymerase.
  2. Chain termination: Upon incorporation into the growing viral DNA chain, the compound delays and completely halts further elongation.

The drug demonstrates high selectivity, inhibiting the DNA polymerase of viruses (including cytomegalovirus and herpes simplex virus) at concentrations hundreds of times lower than those required to suppress human DNA polymerase.

Foscarnet: General Characteristics and Spectrum

Sodium foscarnet (Foscarnetum) is a non-nucleoside DNA polymerase inhibitor and an inorganic pyrophosphate analogue. The drug possesses a broad spectrum of activity against all herpesviruses (including ganciclovir-resistant CMV strains) as well as the human immunodeficiency virus (HIV).

Mechanism of Action and Pharmacokinetics of Foscarnet

Foscarnet targets the viral DNA polymerase in herpesviruses and reverse transcriptase in HIV. Its molecular mechanism involves binding to the pyrophosphate-binding site of the enzyme, blocking the cleavage of pyrophosphate from deoxynucleoside triphosphates. This disrupts nucleotide incorporation into the DNA chain and halts viral nucleic acid synthesis. Its inhibitory effect on viral polymerase is more than 100 times greater than its effect on human enzymes.

Pharmacokinetically, foscarnet is characterized by low oral bioavailability, making intravenous administration necessary. Primary indications include cytomegalovirus retinitis (predominantly in patients with AIDS) and other severe CMV infections.

Frequently asked questions

Which viruses are included in the antiviral spectrum of cidofovir?

The antiviral spectrum of cidofovir includes:

  • Cytomegalovirus (CMV) — viral replication is suppressed.
  • Herpes simplex virus (HSV) — viral DNA polymerase is inhibited.

Achieving an antiviral effect requires drug concentrations hundreds of times lower than those needed to suppress homologous enzymes in healthy human cells.

What specific adverse effects are associated with foscarnet?

A notable adverse effect of foscarnet is marked nephrotoxicity. Because of the high risk of renal injury, this drug is primarily used as a second-line agent.

Indications for switching to foscarnet include:

  • Resistance — failure of preceding therapy.
  • Contraindications to ganciclovir — presence of moderate to severe baseline thrombocytopenia.
What is the main chemical difference between cidofovir and classical nucleosides?

Cidofovir is a nucleotide analogue that already contains a phosphonate group in its structure, bypassing the need for initial phosphorylation by viral enzymes.

Which enzymes activate cidofovir in the body?

Activation of the drug to the diphosphate form occurs exclusively via cellular kinases in both healthy and infected cells.

To which chemical class does foscarnet belong and how is it administered?

Foscarnet is an inorganic pyrophosphate analogue. Due to poor oral bioavailability, it is administered exclusively via intravenous infusion.

What causes resistance to cidofovir?

Resistance to the drug is typically caused by mutations in the viral DNA polymerase gene itself, rather than changes in kinases.

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