Discovered 45 years ago, ribavirin still proves useful as a broad-spectrum
anti-viral drug against different RNA and DNA viruses. Although many cellular and
molecular mechanisms of ribavirin action have been proposed during several decades
of the extensive research, the complete spectrum of its actions is still not fully known.
The direct mechanisms of ribavirin anti-viral action involve RNA polymerase
inhibition and lethal mutagenesis. The main intracellular target of ribavirin action is
inosine 5'-monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in a de
novo synthesis of guanine nucleotides. The inhibition of IMPDH activity leads to
depletion of the guanine nucleotide pool and the consequent attenuation of GTPdependent
cellular processes, inducing cell cycle arrest, and the interruption of DNA
and RNA synthesis. Since these processes are essential for the normal as well as
mitogenic functions of all cells, the inhibition of IMPDH probably represents the
central mechanism of ribavirin action, including its cytotoxic effect. Recent data
suggest that ribavirin may also be effective as an anti-cancer drug. By inhibiting the
eukaryotic translation initiation factor e4E (eIF4E), ribavirin impedes eIF4E-mediated
oncogenic transformation. Additionally, immunomodulatory and immunosuppressive
actions of ribavirin have been shown in different in vivo and in vitro models of
neuroinflammation. Accumulating evidence points to important cell type-specific
differences in response to ribavirin that may arise from cell specific variations in
ribavirin metabolism, as well as the functional status of targeted cells. This chapter
reviews the antiviral, anticancer and anti-inflammatory activities of ribavirin and its
metabolites, and discusses the possible mechanisms of action.
Keywords: Anaemia, Astrocytes, Cancer, Cap structure, Encephalitis, Guanosine
nucleotides, Hepatitis C, Inhibition, Immunomodulation, Immunosuppression,
Leukaemia, Microglia, Multiple sclerosis, Mutagenesis, Nucleoside analogue,
Nucleoside transporters, Oncogenes, Ribavirin, RNA viruses, T-cells.
