Ribavirin (originally also known as Virazole) is a synthetic chemical not found in nature. It was first synthesized in 1970 (Lau, 2002—see hepcassoc.org external link below) at ICN Pharmaceuticals, Inc. (later Valeant Pharmaceuticals International) by chemist Joseph T. Witkowski, under the direction of laboratory director Roland K. Robins. (Robins a purine chemist, had earlier been the inventor of the highly successful purine-analogue pharmaceutical allopurinol).
Ribavirin was discovered as part of a systematic ICN search of antiviral and antitumor activity in synthetic nucleosides. This was inspired in part by discovery (in the 1960s) of antiviral activity from naturally-occurring purine-like nucleoside antibiotics like showdomycin, coformycin, and pyrazomycin. These agents had too much toxicity to be clinically useful (and the antiviral activity of them may be incidental), but they served as the starting point for pharmaceutical chemists interested in antivirals and antimetabolic chemotherapeutic agents.
In 1972 it was reported that ribavirin was active against a variety of RNA and DNA viruses in culture and in animals, without undue toxicity. Ribavirin protected mice against mortality from both A and B strains of influenza, and ICN originally planned to market it as an anti-influenza drug. Results in human trials against experimental influenza infection were mixed, however, and the FDA ultimately did not approve this indication for ribavirin use in humans, thereby causing a severe financial shock to ICN.
Although ICN was allowed in 1980 to market ribavirin, in inhalant form, for RSV infection in children, the U.S. market for this indication was small. By the time oral ribavirin was finally approved by the FDA as part of a combination treatment (with interferon) for hepatitis C in 1998, the original ICN patents on ribavirin itself had expired, and (notwithstanding subsequent patent disputes) ribavirin had become essentially a generic drug.
Future: Other Viral Activities
Experimental data indicate that ribavirin may have useful activity against many viruses of interest, including avian influenza, hepatitis B, polio, measles, Canine distemper and smallpox. Ribavirin is the only known treatment for a variety of viral hemorrhagic fevers, including Lassa fever, Crimean-Congo hemorrhagic fever, and Hantavirus infection. Ribavirin is active in a hamster model of yellow fever, a finding which is not surprising, given the familial relationship of yellow fever and hepatitis C viruses as flaviviridae. Ribavirin is active against other important flaviviridae such as West Nile virus and dengue fever.
Ribavirin's present generic status is expected to slow research into new uses, however.
Further Reading
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