RIBAVIRIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C8H12N4O5
Molecular Weight	244.2047
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=O)C1=NN(C=N1)[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O

InChI

InChIKey=IWUCXVSUMQZMFG-AFCXAGJDSA-N

InChI=1S/C8H12N4O5/c9-6(16)7-10-2-12(11-7)8-5(15)4(14)3(1-13)17-8/h2-5,8,13-15H,1H2,(H2,9,16)/t3-,4-,5-,8-/m1/s1

HIDE SMILES / InChI

Description

Ribavirin is a synthetic nucleoside analogue, which was first discovered and developed in 1970 by researchers from the International Chemical & Nuclear Corporation (ICN), today known as Valeant Pharmaceuticals. Ribavirin was initially approved for use in humans to treat pediatric respiratory syncytial virus infections (RSV). In cell cultures the inhibitory activity of ribavirin for RSV is selective. The mechanism of action is unknown. Reversal of the in vitro antiviral activity by guanosine or xanthosine suggests ribavirin may act as an analogue of these cellular metabolites. There were no other significant advancements in the treatment of hepatitis C until 1998, when the combination of ribavirin and interferon-alpha gained approval. Clinically, ribavirin showed a small, additive antiviral effect in combination with interferon, but its main effect was dose-dependent prevention of virological relapse. The mechanism by which the combination of ribavirin and an interferon product exerts its effects against the hepatitis C virus has not been fully established. However, it could be thorough the inhibition of inosine monophosphate dehydrogenase (IMPDH), which is the key step in de novo guanine synthesis, a requirement for viral replication.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hepatitis C virus NS5B RNA-dependent RNA polymerase 14	Inhibitor 7468	Hepatitis C, Chronic
Inosine-5'-monophosphate dehydrogenase 1 4	Inhibitor 7468	Hepatitis C, Chronic

Conditions

Condition	Modality	Targets	Highest Phase	Product
Respiratory Syncytial Virus Infections 4	Primary	Inosine-5'-monophosphate dehydrogenase 1	Approved 7883	VIRAZOLE
Hepatitis C, Chronic 34	Primary	Inosine-5'-monophosphate dehydrogenase 1 Hepatitis C virus NS5B RNA-dependent RNA polymerase	Approved 7883	COPEGUS
Hepatitis C virus infection (in HIV-infected) 1			Approved (off-label) 8

PubMed

Title	Date	PubMed
Inhibition of vaccinia virus growth by the nucleoside analogue 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole, ribavirin).	1976 Aug	1018177
Synthesis of tetrazole ribonucleosides and their evaluation as antiviral agents.	1976 Feb	1249809
Effect of cytosine, arabinoside, iododeoxyuridine, ethyldeoxyuridine, thiocyanatodeoxyuridine, and ribavirin on tail lesion formation in mice infected with vaccinia virus.	1976 Mar	1257248
Selective inhibition of arthropod-borne and arenaviruses in vitro by 3'-fluoro-3'-deoxyadenosine.	1992 Jun	1365816
Treatment of severe recurrent hepatitis C after liver transplantation with ribavirin plus interferon alpha.	1999 Feb-Mar	10083207
[Effect of ribavirin on dynamics of hepatitis C viremia in interferon alpha-treated patiens with response or no response].	2000 Nov	11132533
Factors influencing ribavirin-induced hemolysis.	2001 Jun	11451176
A rapid assay for evaluation of antiviral activity against coxsackie virus B3, influenza virus A, and herpes simplex virus type 1.	2001 Jun	11377720
In vivo influenza virus-inhibitory effects of the cyclopentane neuraminidase inhibitor RJW-270201.	2001 Mar	11181355
Cyclopentane neuraminidase inhibitors with potent in vitro anti-influenza virus activities.	2001 Mar	11181354
In vitro evaluation of secoiridoid glucosides from the fruits of Ligustrum lucidum as antiviral agents.	2001 Nov	11724241
A preliminary study of erythropoietin for anemia associated with ribavirin and interferon-alpha.	2001 Sep	11569724
Chronic hepatitis C in HIV infection: feasibility and sustained efficacy of therapy with interferon alfa-2b and tribavirin.	2001 Sep 28	11579239
Effect of ribavirin on epididymal sperm count in rat.	2002 Jan	12024964
Ribavirin-induced sperm shape abnormalities in Wistar rat.	2002 Jan 15	11719104
Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children.	2002 Jul	12093990
Nephrotoxicity of interferon alfa-ribavirin therapy for chronic hepatitis C.	2002 Jul	12080234
Identification of active antiviral compounds against a New York isolate of West Nile virus.	2002 Jul	12076755
Evaluation of the antiviral activity against Junin virus of macrocyclic trichothecenes produced by the hypocrealean epibiont of Baccharis coridifolia.	2002 Mar	11914955
Treatment of ribavirin/interferon-induced anemia with erythropoietin in patients with hepatitis C.	2002 May	11981781
Characterization of wild-type and cidofovir-resistant strains of camelpox, cowpox, monkeypox, and vaccinia viruses.	2002 May	11959564
Treatment of acute hepatitis C virus infection with interferon-alpha 2b and ribavirin: case report and review of the literature.	2002 Oct 14	12437778
Hemoglobinuria with ribavirin treatment.	2003 Apr	12642748
Ribavirin reduces clinical signs and pathological changes of experimental autoimmune encephalomyelitis in Dark Agouti rats.	2003 Apr 15	12672002
[Is chronic hepatitis C treatment as efficient in the general population as in randomised trials?].	2003 Aug-Sep	14586246
Normal erythropoietin response in chronic hepatitis C patients with ribavirin-induced anaemia.	2003 Feb	12713065
Posterior segment complications in patients with hepatitis C treated with interferon and ribavirin.	2003 Feb	12578794
Adherence and mental side effects during hepatitis C treatment with interferon alfa and ribavirin in psychiatric risk groups.	2003 Feb	12540795
Successful treatment of giant cell hepatitis with Rebetron (interferon/ribavirin).	2003 Jan	12526974
Synergistic in vitro interactions between alpha interferon and ribavirin against bovine viral diarrhea virus and yellow fever virus as surrogate models of hepatitis C virus replication.	2003 Jul	12821481
The effect of ribavirin and IMPDH inhibitors on hepatitis C virus subgenomic replicon RNA.	2003 Jun 5	12781720
How can we identify better those with recurrent hepatitis C who will respond to therapy? What are the optimal treatment regimen and treatment duration?	2003 Nov	14586905
Rosacea fulminans associated with pegylated interferon alpha-2B and ribavirin therapy.	2003 Oct	14558405

Patents

Sample Use Guides

In Vivo Use Guide

respiratory syncytial virus infection: 20 mg/mL VIRAZOLE (Ribavirin for inhalation solution) as the starting solution in the drug reservoir of the SPAG-2 unit, with continuous aerosol administration for 12-18 hours per day for 3 to 7 days. Using the recommended drug concentration of 20 mg/mL the average aerosol concentration for a 12 hour delivery period would be 190 micrograms/liter of air. Aerosolized VIRAZOLE should not be administered in a mixture for combined aerosolization or simultaneously with other aerosolized medications. Chronic hepatitis C virus infection: The recommended duration of treatment for patients previously untreated with ribavirin and interferon is 24 to 48 weeks. The daily dose of COPEGUS (ribavirin) tablets is 800 mg to 1200 mg administered orally in two divided doses. The dose should be individualized to the patient depending on baseline disease characteristics (eg, genotype), response to therapy, and tolerability of the regimen.

Route of Administration: oral; respiratory

In Vitro Use Guide

To determine the optimal concentration and timing of ribavirin treatment for the inhibition of viral transcription, Human A549 pulmonary type II epithelial cells pretreated (2 h) or posttreated (1 h) with increasing concentrations of ribavirin (from10 to 100 microg/ml) were exposed to pRSV (Respiratory syncytial virus). Total cellular RNA was harvested 36 h later, and the abundance of the 1.1-kb RSV N transcript was measured by Northern blotting. Ribavirin treatment potently inhibited RSV transcription, thereby reducing the level of RSV N transcripts to approximately 13% of levels in nontreated cells. In RSV-infected epithelial cells, ribavirin reduces plaque formation, the release of infectious virions, and F glycoprotein expression.

Name

Type

Language

RIBAVIRIN

Official Name

English

COPEGUS

Brand Name

English

COTRONAK

Brand Name

English

RBV

Common Name

English

RIBAVIRIN [INN]

Common Name

English

1H-1,2,4-TRIAZOLE-3-CARBOXAMIDE, 1-.BETA.-D-RIBOFURANOSYL-

Common Name

English

RIBAVIRIN [HSDB]

Common Name

English

RIBAVIRIN [EMA EPAR]

Common Name

English

SCH 18908

Code

English

SCH-18908

Code

English

NSC-163039

Code

English

RIBAVIRIN BIOPARTNERS

Brand Name

English

RIBAVIRIN [MI]

Common Name

English

RIBAVIRIN TEVA PHARMA B.V.

Brand Name

English

REBETOL

Brand Name

English

RIBAVIRIN MYLAN

Brand Name

English

RIBAVIRIN [VANDF]

Common Name

English

RIBAVIRIN [JAN]

Common Name

English

RIBAVIRIN [MART.]

Common Name

English

RIBAVIRIN [USP]

Common Name

English

RIBAVIRIN [ORANGE BOOK]

Common Name

English

RIBAVIRIN COMPONENT OF PEGINTERFERON

Common Name

English

VIRAZOLE

Brand Name

English

RIBASPHERE

Brand Name

English

RIBAVIRIN [WHO-DD]

Common Name

English

RIBAVIRIN [USAN]

Common Name

English

RIBAVIRIN [EP]

Common Name

English

RIBAVIRIN TEVA

Brand Name

English

1-.BETA.-D-RIBOFURANOSYL-1H-1,2,4-TRIAZOLE-3-CARBOXAMIDE

Common Name

English

RIBAVIRIN [USP-RS]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175466