Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part I: influenza life-cycle and currently available drugs

GASPARINI, R.; AMICIZIA, D.; LAI, PL.; BRAGAZZI, NL.; PANATTO, D.

Considering the compounds targeted against the transcription and replication of vRNA, one of the first de-veloped drug is Ribavirin (Figs. 2, 3) . Ribavirin, also known as the trade name of Virazole, is the guanosine nucleoside analog: 1β-D-ribofuranosyl-1,2,4,-triazole-3-carboxamide. Its mechanism of action is not completely known. However, Inosine 5'-monoposphate dehydrogenase (IMPDH) appears to be the principal target of the molecule [234] . This inhibition diminishes the intracellular concentration of GTP (Guanosine-5'triphosphate), and this would stop viral protein synthesis and limit the vRNA replication. Crotty et al also demonstrated that Ribavirin is a vRNA lethal mutagen, resembling guanosine or adenosine and causing mutations in RNA replication [235] . However, the need of high doses of the drug to have good clinical results have limited the use of Ribavirin as anti-influenza drug, and a recent revision of the literature by Chan-Tack et al. suggests that there are not conclusive results about the beneficial use of Virazole for treatment of influenza [236] . Ribavirin can be administered orally, by aerosolization, rarely by intravenous route [237] . ADR is dependent on the administration route, being extravascular haemolytic anemia if the drug is delivered intravenously, a bronchospasm if aerosolized [216] .