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 7197	Hepatitis C, Chronic
Inosine-5'-monophosphate dehydrogenase 1 4	Inhibitor 7197	Hepatitis C, Chronic

Conditions

Condition	Modality	Targets	Highest Phase	Product
Respiratory Syncytial Virus Infections 4	Primary	Inosine-5'-monophosphate dehydrogenase 1	Approved 7777	VIRAZOLE
Hepatitis C, Chronic 34	Primary	Inosine-5'-monophosphate dehydrogenase 1 Hepatitis C virus NS5B RNA-dependent RNA polymerase	Approved 7777	COPEGUS
Hepatitis C virus infection (in HIV-infected) 1			Approved (off-label) 7

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
Antiviral and antitumor structure-activity relationship studies on tetracyclic eudistomines.	1992 Aug 21	1324318
Selective inhibition of arthropod-borne and arenaviruses in vitro by 3'-fluoro-3'-deoxyadenosine.	1992 Jun	1365816
(+-)-carbocyclic 5'-nor-2'-deoxyguanosine and related purine derivatives: synthesis and antiviral properties.	1992 Jun 12	1319491
Synthesis and antiviral activity of some new S-adenosyl-L-homocysteine derivatives.	1992 Nov 27	1335077
Broad-spectrum antiviral activity of the IMP dehydrogenase inhibitor VX-497: a comparison with ribavirin and demonstration of antiviral additivity with alpha interferon.	2000 Apr	10722482
Antiviral activity of mixed-valence rare earth borotungstate heteropoly blues against influenza virus in mice.	2000 Nov	11227994
Respiratory tract infections caused by respiratory syncytial virus in children. Diagnosis and treatment.	2001 Apr	11404731
Uric acid nephrolithiasis associated with interferon and ribavirin treatment of hepatitis C.	2001 Apr	11330434
Synthesis, mechanism of action, and antiviral activity of a new series of covalent mechanism-based inhibitors of S-adenosyl-L-homocysteine hydrolase.	2001 Aug 16	11495586
Increased mitochondrial toxicity with ribavirin in HIV/HCV coinfection.	2001 Jan 27	11214134
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
The in vitro study of influence of four novel platinum compounds on rodent melanoma cells.	2001 May-Jun	11712733
Antiviral activity and mode of action studies of ribavirin and mycophenolic acid against orthopoxviruses in vitro.	2001 Nov	12018677
Novel carbocyclic nucleosides containing a cyclobutyl ring: adenosine analogues.	2001 Sep	11558606
Management strategies for ribavirin-induced hemolytic anemia in the treatment of hepatitis C: clinical and economic implications.	2001 Sep-Oct	11705128
[ROC curve analysis of factors predictive of response to treatment with interferon plus ribavirin in patients with chronic hepatitis C relapse after previous interferon treatment].	2002 Dec	12587043
[Novel mode of action of ribavirin (Rebetol), a drug for the treatment of chronic hepatitis C: inducting the mutation of RNA viruses].	2002 Dec	12528471
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
Cidofovir in the treatment of poxvirus infections.	2002 Jul	12076747
1-beta-D-arabinofuranosylcytosine inhibits borna disease virus replication and spread.	2002 Jun	12021360
Interferon-alpha induced transient thyroid dysfunction in hepatitis C.	2002 Mar	12185880
Combination treatment of influenza A virus infections in cell culture and in mice with the cyclopentane neuraminidase inhibitor RWJ-270201 and ribavirin.	2002 May	12011541
Treatment of ribavirin/interferon-induced anemia with erythropoietin in patients with hepatitis C.	2002 May	11981781
Mechanism of action of ribavirin in the combination treatment of chronic HCV infection.	2002 May	11981750
Heterocyclic nucleoside analogues: design and synthesis of antiviral, modified nucleosides containing isoxazole heterocycles.	2002 May 20	11992785
Comparison of colorimetric, fluorometric, and visual methods for determining anti-influenza (H1N1 and H3N2) virus activities and toxicities of compounds.	2002 Oct	12367731
Treatment of acute hepatitis C virus infection with interferon-alpha 2b and ribavirin: case report and review of the literature.	2002 Oct 14	12437778
U.S. veterans' experience with rebetron in a nonstudy environment: success or failure?	2002 Sep	12358260
Anemia in the treatment of hepatitis C virus infection.	2003	14582000
Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency.	2003 Aug	12897097
Combination therapy in the treatment of chronic viral hepatitis and prevention of hepatocellular carcinoma.	2003 Aug	12860172
Synthesis of 1,2,3-triazolo-carbanucleoside analogues of ribavirin targeting an HCV in replicon.	2003 Aug 15	12901908
[Is chronic hepatitis C treatment as efficient in the general population as in randomised trials?].	2003 Aug-Sep	14586246
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
In vitro activity of potential anti-poxvirus agents.	2003 Jan	12615301
Potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections.	2003 Jan	12615299
[52-year-old patient with subcutaneous space-occupying lesion in immunosuppression].	2003 Jun	14567110
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
[Use of erythropoietin in the treatment of anemia induced by ribavirin/interferon in patients with hepatitis C].	2003 Oct	14568602
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