Inhibitor of Viral RNA Synthesis: Ribavirin
Ribavirin is another analog of the nucleoside guanosine. Unlike acyclovir, which replacesthe ribose moiety with an hydroxymethyl acyclic side chain, ribavirin differs from guanosine in that the base ring is incomplete and open. Like other purine nucleoside analogs, ribavirin must be phosphorylated to mono-, di-, and triphosphate forms. It is active against a broad range of viruses in vitro, but its in vivo activity is limited. The mechanism of the antiviral ef-fect of ribavirin is not as clear as that of acyclovir. The triphosphate is an inhibitor of RNA polymerase and it also depletes cellular stores of guanine by inhibiting inosine monophos-phate dehydrogenase, an enzyme important in the synthetic pathway of guanosine. Still an-other mode of action is by decreasing synthesis of the mRNA 5’ cap because of interference with both guanylation and methylation of the nucleic acid base.
Aerosol administration enables ribavirin to reach concentrations in respiratory secre-tions up to ten times greater than necessary to inhibit viral replication and substantially higher than those achieved with oral administration. Problems encountered with aerosolized ribavirin include precipitation of the agent in tubing used for administration and exposure of health care personnel.
Ribavirin is somewhat beneficial if given early by aerosol to infants who are infected with respiratory syncytial virus. Oral and intravenous forms have been used for patients with Lassa fever, although studies have been limited. In a recent trial of hantavirus treat-ment, ribavirin was ineffective. The oral form has limited activity against hepatitis C as monotherapy but provides additional benefit when combined with interferon alpha. A re-versible anemia has been associated with oral administration of ribavirin.