Mechanism of Action of Ribavirin: An Antiviral Drug of Military Importance,

Abstract : Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a nucleoside analogue having broad spectrum antiviral activity against both DNA and RNA viruses (18). A variety of specific effects on host cell metabolism have been attributed to ribavirin or its metabolites. For example, ribavirin is reported to be a strong inhibitor of thymidine phosphorylation (6) and its 5'-monophosphate derivative (RMP) is a potent competitive inhibitor of inosine-5'-phosphate dehydrogenase (19). Ribavirin is also reported to decrease DNA, RNA and protein synthesis and reduce the size of the cellular guanosine-5'-triphosphate pool (5,12). Numerous other reports, however, contradict many of the alleged cellular effects of ribavirin (2,14,15,17). As a result, the pharmacological mechanism of action of ribavirin remains obscure. It is not yet clear whether this compound is specifically antiviral or whether it inhibits virus replication as a result of its effects on host cellular metabolism. The study reported here attempts to clarify the mode and specificity of action of ribavirin. We have examined its effects on cellular metabolism and on the replication of Venezualan equine encephalomyelitis virus (VEE) grown in BHK-21 cells. (Author)