Guanosine antiviral analogues

Fig. 7. Adenosine and guanosine analogues with both RNA and DNA antiviral effectiveness.

Ribavirin is a synthetic guanosine analogue that possesses broad antiviral inhibitory activity against many viruses, including influenza A and B, parainfluenza, RS V, HCV, HIV-1, and various herpesviruses, arenaviruses, and paramyxoviruses. Its exact mechanism of action has not been fully elucidated however, it appears to inhibit the synthesis of viral mRNA through an effect on nucleotide pools. Following absorption, host cell enzymes convert ribavirin to its monophosphate, diphosphate, and triphosphate forms. Ribavirin monophosphate... 

Ribavirin This guanosine analogue was first used experimentally by o. Reichard et al. (1991) and in chronic hepatitis C by J. Andersson et al. (1991). It is rapidly absorbed and distributed in the body, but is excreted slowly (half-life 79 hours). The bioavailability is 45-65%. As a monotherapy, it only leads to a decrease in transaminases and a slight improvement in histological activity. Ribavirin may not exhibit a direct antiviral effect, but can trigger a favourable response to interferon. When combined with IFN, ribavirin proved far more efficacious in chronic hepatitis C (immunomo-dulation ) without any increase in the typical side effects of IFN. (49, 51, 53) (s. p. 707)... 

Oral guanosine analogue with antiviral activity against variety of RNA and DNA viruses. For HCV infections, combination of ribavirin plus interferon improves virologic response compared to interferon monotherapy. 

Oxanosine, a novel guanosine analogue antibiotic has been phosphorylated according to the Yoshikawa procedure to yield (17) and evaluated for in vitro antiviral activity against HIV proliferation. Compound (17) reduced the number of HIV particles in CEM cells to almost the same level as ddl. 

Mechanism of Action. The drug is a nueleoside analogue structurally related to guanosine having distinct antiviral activity against HIV-1. Its acts as an inhibitor of viral reverse transcryptase and is under investigation in the treatment of AIDS. 

Ribavirin, a guanosine analogue, has broad-spectrum antiviral aotivity against both DNA and RNA viruses (52,53). It is phosphorylated by adenosine kinase to the triphosphate, resulting in the inhibition of viral specific RNA polymerase, disrupting messenger RNA and nucleio aoid synthesis. 

Figure 23.17 Analogues of guanosine used in antiviral therapy.

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