Ribavirin (Molecule of the Month for December 2015)
Copegus, Rebetol, Ribasphere, Vilona, Virazole
Ribavirin is an anti-viral drug which is active against a number of DNA and RNA viruses. It is a member of the nucleoside antimetabolite drugs that interfere with duplication of viral genetic material. Though not effective against all viruses, ribavirin has important activities against influenzas, flaviviruses and agents of many viral hemorrhagic fevers.
Ribavirin is a pro-drug, meaning that it is a chemical precursor for the actual phamacologically active molecule. When the pro-drug is administered, the body converts it into the desired chemical. Ribavirin is activated by cellular kinases which change it into the 5' triphosphate nucleotide. In this form it interferes with aspects of RNA metabolism related to viral reproduction.
Ribavirin's carboxamide group can made 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. Ribavirin 5' mono- di- and tri-phosphates, in addition, are all inhibitors of certain viral RNA-dependent RNA polymerases which are a feature of RNA viruses (save for retroviruses). Neither of these mechanisms explains ribavirin's effect on many DNA viruses, which is more of a mystery. Ribavirin 5'-monophosphate inhibits cellular inosine monophosphate dehydrogenase, thereby depleting intracellular pools of GTP. This mechanism may be useful in explaining the drug's general cytotoxic and anti-DNA replication effect (i.e. its toxicity) as well as some effect on DNA viral replication.
Formal Chemical Name (IUPAC)
Update by Karl Harrison
(Molecule of the Month for December 2015 )