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Acting on RNA and DNA viruses

The antiviral agents active against DNA and RNA viruses are ribavirin and foscarnet.

 

Ribavirin

Ribavirin is a synthetic nucleoside with a chemical structure including a ribose and a triazole ring. It has an antiviral extended-spectrum against DNA and RNA viruses.

Ribavirin is converted into mono, di and triphosphate derivatives. It has many mechanisms of action, among which inhibition of inosine 5 '- monophosphate (IMP) dehydrogenase, responsible of the conversion of IMP into xanthosine 5 '- monophosphate, leading to the synthesis of RNA.

Ribavirin (Rebetol*, Copegus*) is prescribed as aerosol in the treatment of infections with respiratory syncitial virus (RSV). Particularly when used as aerosol, special precautions must be taken to ensure a good ventilation of the room where the patient is to avoid the contamination of medical staff, in particular women likely to be pregnant, because ribavirin is teratogenic and has a very long half-life because of its accumulation in erythrocytes.

Ribavirin is used by oral route in combination with interferon alfa-2b in the treatment of chronic hepatitis C, combination giving interesting results.

Ribavirin being teratogenic at very low doses, precautions must be taken to avoid a pregnancy in women treated or partner of a treated man.

Foscarnet

Foscarnet is an inhibitor of the viral DNA polymerase having a particular chemical structure: it is a trisodium phosphonoformate without analogy with purine and pyrimidine bases.

Foscarnet inhibits the multiplication of DNA viruses such as Herpes group: Herpes simplex, chicken pox, herpes zoster, Epstein-Barr, cytomegalovirus and hepatitis B virus. Foscarnet inhibits also HIV reverse transcriptase.

Concerning pharmacokinetics, foscarnet has a short plasma half-life and is eliminated by the kidney. In patients with renal impairment a reduction of its dosage is necessary.

The principal indication of foscarnet (Foscavir*) is the treatment of cytomegalovirus retinitis. This retinitis is observed especially in patients with HIV infections. It can be also used in the treatment of the mucocutaneous infections with herpes simplex virus resistant or insensitive to aciclovir in immunocompromised patients.

Among adverse effects of foscarnet, one can quote renal impairment, hematopoietic disorders (anemia, leukopenia) and hypocalcemia. This last is explained by the fact that foscarnet is a chelating agent of calcium and other elements like magnesium, copper and zinc. The chelation can explain at least partially its pharmacologic effect on DNA polymerase.

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