DNA viruses
Neither of these mechanisms explains ribavirins effect on many DNA viruses, which is more of a mystery, especially given the complete inactivity of ribavirins 2 deoxyribose analogue, which suggests that the drug functions only as an RNA nucleoside mimic, and never a DNA nucleoside mimic. Ribavirin 5-monophosphate inhibits cellular inosine monophosphate dehydrogenase, thereby depleting intracellular pools of GTP. History
Ribavirin was first made in 1972 under the national cancer institutes Virus-Cancer program. This was done by researchers from International Chemical and Nuclear Corporation including Roberts A. Smith, Joseph T. Witkovski and Roland K. Robins. It was reported that ribavirin was active against a variety of RNA and DNA viruses in culture and in animals, without undue toxicity in the context of cancer chemotherapies. By the late 1970s, the Virus-Cancer program was widely considered a failure, and the drug development was abandoned. Names
Ribavirin is the INN and USAN, whereas tribavirin is the BAN. Brand names of generic forms include Copegus, Ribasphere, Rebetol. Derivatives
Ribavirin is possibly best viewed as a ribosyl purine analogue with an incomplete purine 6-membered ring. This structural resemblance historically prompted replacement of the 2 nitrogen of the triazole with a carbon (which becomes the 5 carbon in an imidazole), in an attempt to partly "fill out" the second ring--- but to no great effect. Such 5 imidazole riboside derivatives show antiviral activity with 5 hydrogen or halide, but the larger the substituent, the smaller the activity, and all proved less active than ribavirin.
Note that two natural products were already known with this imidazole riboside structure: substitution at the 5 carbon with OH results in pyrazofurin, an antibiotic with antiviral properties but unacceptable toxicity, and replacement with an amino group results in the natural purine synthetic precursor 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), which has only modest antiviral properties. Taribavirin
The most successful ribavirin derivative to date is the 3-carboxamidine derivative of the parent 3-carboxamide, first reported in 1973 by J. T. Witkowski et al., and now called taribavirin (former names "viramidine" and "ribamidine"). This drug shows a similar spectrum of antiviral activity to ribavirin, which is not surprising as it is now known to be a pro-drug for ribavirin. Taribavirin, however, has useful properties of less erythrocyte-trapping and better liver-targeting than ribavirin. The first property is due to taribavirins basic amidine group which inhibits drug entry into RBCs, and the second property is probably due to increased concentration of the enzymes which convert amidine to amide in liver tissue. Taribavirin completed phase III human trials in 2012. References
External links
"Ribavirin". Drug Information Portal. U.S. National Library of Medicine.