Adverse effects
The medication has two FDA "black box" warnings: One raises concerns that use before or during pregnancy by either sex may result in birth defects in the baby, and the other is regarding the risk of red blood cell breakdown.Ribavirin should not be given with zidovudine because of the increased risk of anemia; concurrent use with didanosine should likewise be avoided because of an increased risk of mitochondrial toxicity. Mechanisms of action
It is a guanosine (ribonucleic) analog used to stop viral RNA synthesis and viral mRNA capping, thus, it is a nucleoside inhibitor. Ribavirin is a prodrug, which when metabolized resembles purine RNA nucleotides. In this form, it interferes with RNA metabolism required for viral replication. Over five direct and indirect mechanisms have been proposed for its mechanism of action. The enzyme inosine triphosphate pyrophosphatase (ITPase) dephosphorylates ribavirin triphosphate in vitro to ribavirin monophosphate, and ITPase reduced enzymatic activity present in 30% of humans potentiates mutagenesis in hepatitis C virus. RNA viruses
Ribavirins amide group can make the native nucleoside drug resemble adenosine or guanosine, depending on its rotation. For this reason, when ribavirin is incorporated into RNA, as a base analog of either adenine or guanine, it pairs equally well with either uracil or cytosine, inducing mutations in RNA-dependent replication in RNA viruses. Such hypermutation can be lethal to RNA viruses.
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.