Ribavirin (original) (raw)

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Summary

Ribavirin is a guanosine nucleoside used to treat some forms of Hepatitis C.

Brand Names

Ibavyr, Rebetol, Virazole

Generic Name

Ribavirin

DrugBank Accession Number

DB00811

Background

Producing a broad-spectrum activity against several RNA and DNA viruses, Ribavirin is a synthetic guanosine nucleoside and antiviral agent that interferes with the synthesis of viral mRNA. It is primarily indicated for use in treating hepatitis C and viral hemorrhagic fevers. HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients 9. It is reported that ribavirin might be only effective in early stages of viral hemorrhagic fevers including Lasser fever, Crimean-Congo hemorrhagic fever, Venezuelan hemorrhagic fever, and Hantavirus infection. Ribavirin is a prodrug that is metabolized into nucleoside analogs that blocks viral RNA synthesis and viral mRNA capping. Before the development of newer drugs, ribavirin and Peginterferon alfa-2a/Peginterferon alfa-2b dual therapy was considered the first-generation and standard antiviral treatment 5. The dual therapy was administered for 48 weeks in patients with genotype 1, 4, 5, and 6, and 24 weeks in patients with genotype 2 and 3 5. Newer drugs developed as Hepatitis C viral infection treatments can be used to reduce or eliminate the use of ribavirin, which are associated with serious adverse effects. They also improve therapeutic efficacy in patients with failed Peginterferon alfa-2a/Peginterferon alfa-2b and ribavirin-based therapy. The potential use of ribavirin as a treatment for acute myeloid leukemia is currently under investigation.

According to 2017 American Association for the Study of Liver Diseases (AASLD) and 2015 consensus guidelines from the Canadian Association for the Study of the Liver (CASL), ribavirin is typically used as an adjunct therapy to various first-line and second-line combination therapies recommended for each genotypes. Ribavirin is added to decrease relapse rates by accelerating viral clearance early in the treatment course 7. When used to treat Hepatitis C virus (HCV) infections, it is always used as a part of combination therapies as ribavirin monotherapy is not efficacious in the treatment of chronic hepatitis C infection 6. Additionally, including ribavirin in the regimen can increase the risk of anemia.

In HCV genotye 1/2/3/4/5/6 patients, ribavirin can be used in combination therapy involving Daclatasvir and Sofosbuvir, Eplusa (Sofosbuvir, Velpatasvir), Harvoni (Sofosbuvir, Ledipasvir), Simeprevir and Sofosbuvir, Viekira Pak (Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir), Technivie (Ritonavir, Ombitasvir, Paritaprevir) and Zepatier (Elbasvir, Grazoprevir). Addition of weight-based ribavirin to Technivie therapy increased sustained virologic response after 12 weeks of daily therapy (SVR12) from 90% to 97% in patients with HCV genotype 1a and 90.9% to 100% in HCV genotype 4 patients 9. Zepatier therapy along with ribavirin improved SVR in HCV genotype 5 patients. Combination therapy of ribavirin and Peginterferon alfa-2a results in the SVR of 44% in patients with genotype 1 infection and 70% in patients with genotype 2-6. The inclusion of ribavirin in the combination therapies depend on individual patient's profile, for example if HCV genotype 3 patient has a Y93H genetic variant and compensated cirrhosis.

Type

Small Molecule

Groups

Approved

Structure

Weight

Average: 244.2047
Monoisotopic: 244.080769514

Chemical Formula

C8H12N4O5

Synonyms

• 1-beta-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide
• 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide
• RBV
• Ribavirin
• Ribavirina
• Ribavirine
• Ribavirinum
• Tribavirin

External IDs

• ICN 1229
• SCH 18908
• SCH-18908

Indication

Indicated for the treatment of chronic Hepatitis C virus (HCV) infection in combination with other antiviral agents with the intent to cure or achieve a sustained virologic response (SVR). Typically added to improve SVR and reduce relapse rates 6.

The addition of ribavirin in Technivie therapy indicated for treating HCV genotype 1a and 4 infections is recommended in patients with or without cirrhosis.

Resistance: viral genetic determinants resulting in variable response to ribavirin therapy has not been yet determined.

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Associated Conditions

Contraindications & Blackbox Warnings

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Pharmacodynamics

Ribavirin mediates direct antiviral activity against a number of DNA and RNA viruses by increasing the mutation frequency in the genomes of several RNA viruses. It is a member of the nucleoside antimetabolite drugs that interfere with duplication of the viral genetic material. The drug inhibits the activity of the enzyme RNA dependent RNA polymerase, due to its resemblence to building blocks of the RNA molecules.

Mechanism of action

Ribavirin is reported to have several mechanism of actions that lead to inhibition of viral RNA and protein synthesis. After activation by adenosine kinase to ribavirin mono-, di-, and triphosphate metabolites. Ribavirin triphosphate (RTP) is the predominant metabolite which directly inhibits viral mRNA polymerase by binding to the nucleotide binding site of the enzyme. This prevents the binding of the correct nucleotides, leading to a reduction in viral replication or to the production of defective virions 7. RTP also demonstrates an inhibitory action on viral mRNA guanylyltransferase and mRNA 2′-O-methyltransferase of dengue virus. Inhibition of these enzymes disrupts the posttranslational capping of the 5′ end of viral mRNA through ribavirin being incorporated at the 5′ end in place of guanosine and preventing the cap methylation step.

Inhibition of host inosine monophosphate dehydrogenase (IMPDH) and subsequent depletion of GTP pool is proposed to be another mechanism of action of ribavirin. IMPDH catalyzes the rate-limiting step where inosine 5′-monophosphate is converted to xanthine monophosphate during guanosine monophosphate (GMP) synthesis. GMP is later converted to guanosine triphoshpate (GTP). Ribavirin monophosphate mimics inosine 5′-monophosphate and acts as a competitive inhibitor of IMPDH. Inhibited de novo synthesis of guanine nucleotides and decreased intracellular GTP pools leads to a decline in viral protein synthesis and limit replication of viral genomes 7.

Ribavirin acts as a mutagen in the target virus to cause an 'error catastrophe' due to increased viral mutations. RTP pairs with cytidine triphosphate or uridine triphosphate with equal efficiency and to block HCV RNA elongation. It causes premature termination of nascent HCV RNA and increases mutagenesis by producing defective virions 7.

Ribavirin also exerts an immunomodulatory action of the host to the virus by shifting a Th2 response in favor of a Th1 phenotype. Th2 response and production of type 2 cytokines such as IL-4, IL-5, and IL-10 stimulates the humoral response which enhances immunity toward the virus 7. Ribavirin enhanced induction of interferon-related genes, including the interferon-α receptor, and down-regulation of genes involved in interferon inhibition, apoptosis, and hepatic stellate cell activation in vitro 6.

Absorption

Ribavirin is reported to be rapidly and extensively absorbed following oral administration. The average time to reach Cmax was 2 hours after oral administration of 1200 mg ribavirin Label. The oral bioavailability is 64% following a single oral dose administration of 600mg ribavirin 10.

Volume of distribution

Ribavirin displays a large volume of distribution Label.

Protein binding

No protein binding reported 10.

Metabolism

First and as a step required for activation, ribavirin is phosphorylated intracellularly by adenosine kinase to ribavirin mono-, di-, and triphosphate metabolites. After activation and function, ribavirin undergoes two metabolic pathways where it is reversibly phosphorlyated or degraded via deribosylation and amide hydrolysis to yield a triazole carboxylic acid metabolite. In vitro studies indicate that ribavirin is not a substrate of CYP450 enzymes 10.

Route of elimination

The metabolites of ribavirin are renally excreted. After the oral administration of 600mg radiolabeled ribavirin, approximately 61% of the drug was detected in the urine and 12% was detected in the feces. 17% of administered dose was in unchanged form 10.

Half-life

The terminal half-life of ribavirin following administration of a single oral dose of 1200 mg is about 120 to 170 hours Label.

Clearance

The total apparent clearance rate after a single oral dose administration of 1200 mg ribavirin is 26L/h Label.

Adverse Effects

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Toxicity

Rivabirin and PEG-Interferon Alfa-2A dual therapy is associated with flu-like symptoms, depression, suicide, insomnia, irritability, relapse of drug abuse/overdose, hepatic decompensation in 2% of HIV co-infected patients and bacterial infections each occurring at a frequency of less than 1%. Ribavirin-induced anemia is a dose-dependent adverse effect where reduced hemoglobin levels can be seen within the first 1-2 weeks in therapy. The mechanism of ribavirin-induced anemia has been shown to involve reductions in reticulocyte counts and erythrocyte Na-K pump activity, and increases in K-Cl cotransport, membrane bound IgG, and C3, and erythrocyte band 3 6. Oral LD50 in rats is 2700 mg/kg. Intraperitoneal LD50 in mouse is 1300 mg/kg. Potential carcinogenic effects of ribavirin to humans cannot be yet excluded as it demonstrates mutagenic activity in the in vitro mouse lymphoma assay.

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Food Interactions

• Avoid alcohol. Ribavirin is used to treat chronic hepatitis C infection; ingesting alcohol may worsen this infection.
• Take with food. Taking ribavirin with a high-fat meal slows the absorption and increases the AUC and Cmax of ribavirin.

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Product Images

International/Other Brands

Rebretron / Ribamide / Vilona (Valeant) / Viramid (Il Sung) / Virazide (Grossman)

Brand Name Prescription Products

Generic Prescription Products

Mixture Products

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Virazole	Ribavirin (0.1 g/1mL)	Liquid	Intravenous	Legacy Pharmaceuticals Switzerland GmbH	2017-12-06	Not applicable

ATC Codes

J05AP01 — Ribavirin

• J05AP — Antivirals for treatment of HCV infections
• J05A — DIRECT ACTING ANTIVIRALS
• J05 — ANTIVIRALS FOR SYSTEMIC USE
• J — ANTIINFECTIVES FOR SYSTEMIC USE

Drug Categories

• Anti-Infective Agents
• Antiinfectives for Systemic Use
• Antimetabolites
• Antiviral Agents
• Antivirals for Systemic Use
• Antivirals for treatment of HCV infections
• Direct Acting Antivirals
• Drugs that are Mainly Renally Excreted
• Noxae
• Nucleic Acids, Nucleotides, and Nucleosides
• Nucleoside Analog Antiviral
• Nucleosides
• Nucleosides and Nucleotides
• Ribonucleosides
• Toxic Actions
• Treatments for Hepatitis C

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as triazole ribonucleosides and ribonucleotides. These are nucleoside derivatives containing a ribose (or deoxyribose) moiety which is N-glycosylated to a triazole. Nucleotides have a phosphate group linked to the C5 carbon of the ribose (or deoxyribose) moiety.

Kingdom

Organic compounds

Super Class

Nucleosides, nucleotides, and analogues

Class

Triazole ribonucleosides and ribonucleotides

Sub Class

Not Available

Direct Parent

Triazole ribonucleosides and ribonucleotides

Alternative Parents

Glycosylamines / Pentoses / 2-heteroaryl carboxamides / Triazoles / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Primary carboxylic acid amides / Oxacyclic compounds / Azacyclic compounds / Primary alcohols / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives show 5 more

Substituents

1,2,4-triazole / 2-heteroaryl carboxamide / Alcohol / Aromatic heteromonocyclic compound / Azacycle / Azole / Carboxamide group / Carboxylic acid derivative / Glycosyl compound / Heteroaromatic compound / Hydrocarbon derivative / Monosaccharide / N-glycosyl compound / N-ribosyl-1,2,4-triazole / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organoheterocyclic compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Oxacycle / Pentose monosaccharide / Primary alcohol / Primary carboxylic acid amide / Secondary alcohol / Tetrahydrofuran / Triazole show 18 more

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

monocarboxylic acid amide, aromatic amide, 1-ribosyltriazole (CHEBI:63580)

Affected organisms

• Hepatitis B virus
• Hepatitis C virus, RSV and other RNA/DNA viruses

UNII

49717AWG6K

CAS number

36791-04-5

InChI Key

IWUCXVSUMQZMFG-AFCXAGJDSA-N

InChI

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

IUPAC Name

1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide

SMILES

NC(=O)C1=NN(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O

Synthesis Reference

US3798209

General References

1. Sidwell RW, Bailey KW, Wong MH, Barnard DL, Smee DF: In vitro and in vivo influenza virus-inhibitory effects of viramidine. Antiviral Res. 2005 Oct;68(1):10-7. [Article]
2. Sidwell RW, Huffman JH, Khare GP, Allen LB, Witkowski JT, Robins RK: Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide. Science. 1972 Aug 25;177(4050):705-6. [Article]
3. Alvarez D, Dieterich DT, Brau N, Moorehead L, Ball L, Sulkowski MS: Zidovudine use but not weight-based ribavirin dosing impacts anaemia during HCV treatment in HIV-infected persons. J Viral Hepat. 2006 Oct;13(10):683-9. [Article]
4. Bani-Sadr F, Carrat F, Pol S, Hor R, Rosenthal E, Goujard C, Morand P, Lunel-Fabiani F, Salmon-Ceron D, Piroth L, Pialoux G, Bentata M, Cacoub P, Perronne C: Risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus-coinfected patients during interferon plus ribavirin-based therapy. J Acquir Immune Defic Syndr. 2005 Sep 1;40(1):47-52. [Article]
5. Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13. [Article]
6. Martin P, Jensen DM: Ribavirin in the treatment of chronic hepatitis C. J Gastroenterol Hepatol. 2008 Jun;23(6):844-55. doi: 10.1111/j.1440-1746.2008.05398.x. [Article]
7. Te HS, Randall G, Jensen DM: Mechanism of action of ribavirin in the treatment of chronic hepatitis C. Gastroenterol Hepatol (N Y). 2007 Mar;3(3):218-25. [Article]
8. Huggins JW: Prospects for treatment of viral hemorrhagic fevers with ribavirin, a broad-spectrum antiviral drug. Rev Infect Dis. 1989 May-Jun;11 Suppl 4:S750-61. [Article]
9. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
10. FDA Approved Drug Products: Rebetol (ribavirin) oral capsules [Link]

External Links

Human Metabolome Database

HMDB0014949

KEGG Drug

D00423

PubChem Compound

37542

PubChem Substance

46505883

ChemSpider

34439

BindingDB

50154375

RxNav

9344

ChEBI

63580

ChEMBL

CHEMBL1643

ZINC

ZINC000001035331

Therapeutic Targets Database

DNC001210

PharmGKB

PA451241

PDBe Ligand

RBV

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Ribavirin

PDB Entries

3sfu / 4pb1 / 5axd / 8tz1

FDA label

MSDS

Clinical Trials

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Manufacturers

• Schering plough research institute
• Three rivers pharmaceuticals llc
• Aurobindo pharma ltd
• Sandoz inc
• Teva pharmaceuticals usa inc
• Zydus pharmaceuticals usa inc
• Valeant pharmaceuticals international
• Schering corp
• Hoffmann la roche inc

Packagers

• Amerisource Health Services Corp.
• Aurobindo Pharma Ltd.
• Ben Venue Laboratories Inc.
• Cadila Healthcare Ltd.
• DSM Corp.
• F Hoffmann-La Roche Ltd.
• Legacy Pharmaceuticals Packaging LLC
• Mallinckrodt Inc.
• Medisca Inc.
• Par Pharmaceuticals
• Patheon Inc.
• Physicians Total Care Inc.
• Prx Pharmaceuticals
• Richmond Pharmacy
• Sandoz
• Schering Corp.
• Schering-Plough Inc.
• Teva Pharmaceutical Industries Ltd.
• Three Rivers Pharmaceuticals LLC
• Valeant Ltd.
• Warrick Pharmaceuticals Corp.
• Zydus Pharmaceuticals

Dosage Forms

Prices

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
CA2365412	No	2002-09-17	2018-12-21
CA2287056	No	2000-08-15	2018-12-21
US6150337	No	2000-11-21	2017-11-21
US6172046	Yes	2001-01-09	2018-03-21
US6177074	Yes	2001-01-23	2017-05-01
US6461605	Yes	2002-10-08	2017-05-01
US6472373	Yes	2002-10-29	2018-03-21
US6524570	Yes	2003-02-25	2017-05-01
US6790837	Yes	2004-09-14	2023-10-05

State

Solid

Experimental Properties

Predicted Properties

Predicted ADMET Features

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Mass Spec (NIST)

Not Available

Spectra

Chromatographic Properties

Collision Cross Sections (CCS)

Targets

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Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

General Function

Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors

Specific Function

Dna binding

Gene Name

IMPDH1

Uniprot ID

P20839

Uniprot Name

Inosine-5'-monophosphate dehydrogenase 1

Molecular Weight

55405.365 Da

References

1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
2. Gish RG: Treating HCV with ribavirin analogues and ribavirin-like molecules. J Antimicrob Chemother. 2006 Jan;57(1):8-13. Epub 2005 Nov 17. [Article]
3. McHutchison JG, Shiffman ML, Cheung RC, Gordon SC, Wright TL, Pottage JC Jr, McNair L, Ette E, Moseley S, Alam J: A randomized, double-blind, placebo-controlled dose-escalation trial of merimepodib (VX-497) and interferon-alpha in previously untreated patients with chronic hepatitis C. Antivir Ther. 2005;10(5):635-43. [Article]
4. Leyssen P, De Clercq E, Neyts J: The anti-yellow fever virus activity of ribavirin is independent of error-prone replication. Mol Pharmacol. 2006 Apr;69(4):1461-7. Epub 2006 Jan 18. [Article]
5. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Kind

Protein

Organism

HPIV-2

Pharmacological action

Yes

Actions

Antagonist

General Function

Rna-directed rna polymerase activity

Specific Function

Displays RNA-directed RNA polymerase, mRNA guanylyl transferase, mRNA (guanine-N(7)-)-methyltransferase and poly(A) synthetase activities. The viral mRNA guanylyl transferase displays a different b...

Gene Name

L

Uniprot ID

P26676

Uniprot Name

RNA-directed RNA polymerase L

Molecular Weight

256380.115 Da

References

1. Eriksson B, Helgstrand E, Johansson NG, Larsson A, Misiorny A, Noren JO, Philipson L, Stenberg K, Stening G, Stridh S, Oberg B: Inhibition of influenza virus ribonucleic acid polymerase by ribavirin triphosphate. Antimicrob Agents Chemother. 1977 Jun;11(6):946-51. doi: 10.1128/aac.11.6.946. [Article]

Kind

Protein

Organism

DENV-2

Pharmacological action

Yes

Actions

Inhibitor

Ribavirin's effects on genome polyprotein may stem from its inhibition of the mRNA 2'-O-methyltransferase domain.

General Function

Structural molecule activity

Specific Function

Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA.prM acts as a chaperone for envelope protein E during intracellular vi...

Gene Name

Not Available

Uniprot ID

P12823

Uniprot Name

Genome polyprotein

Molecular Weight

379216.195 Da

References

1. Benarroch D, Egloff MP, Mulard L, Guerreiro C, Romette JL, Canard B: A structural basis for the inhibition of the NS5 dengue virus mRNA 2'-O-methyltransferase domain by ribavirin 5'-triphosphate. J Biol Chem. 2004 Aug 20;279(34):35638-43. doi: 10.1074/jbc.M400460200. Epub 2004 May 19. [Article]
2. Chang J, Schul W, Butters TD, Yip A, Liu B, Goh A, Lakshminarayana SB, Alonzi D, Reinkensmeier G, Pan X, Qu X, Weidner JM, Wang L, Yu W, Borune N, Kinch MA, Rayahin JE, Moriarty R, Xu X, Shi PY, Guo JT, Block TM: Combination of alpha-glucosidase inhibitor and ribavirin for the treatment of dengue virus infection in vitro and in vivo. Antiviral Res. 2011 Jan;89(1):26-34. doi: 10.1016/j.antiviral.2010.11.002. Epub 2010 Nov 10. [Article]
3. Pires de Mello CP, Drusano GL, Rodriquez JL, Kaushik A, Brown AN: Antiviral Effects of Clinically-Relevant Interferon-alpha and Ribavirin Regimens against Dengue Virus in the Hollow Fiber Infection Model (HFIM). Viruses. 2018 Jun 9;10(6). pii: v10060317. doi: 10.3390/v10060317. [Article]

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

General Function

Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth (PubMed:7763314, PubMed:7903306). Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism (PubMed:14766016). It may also have a role in the development of malignancy and the growth progression of some tumors

Specific Function

Dna binding

Gene Name

IMPDH2

Uniprot ID

P12268

Uniprot Name

Inosine-5'-monophosphate dehydrogenase 2

Molecular Weight

55804.495 Da

References

1. Markland W, McQuaid TJ, Jain J, Kwong AD: Broad-spectrum antiviral activity of the IMP dehydrogenase inhibitor VX-497: a comparison with ribavirin and demonstration of antiviral additivity with alpha interferon. Antimicrob Agents Chemother. 2000 Apr;44(4):859-66. [Article]
2. Shah CP, Kharkar PS: Newer human inosine 5'-monophosphate dehydrogenase 2 (hIMPDH2) inhibitors as potential anticancer agents. J Enzyme Inhib Med Chem. 2018 Dec;33(1):972-977. doi: 10.1080/14756366.2018.1474211. [Article]

Kind

Protein

Organism

Influenza A virus (strain A/Beijing/11/1956 H1N1)

Pharmacological action

Unknown

Actions

Inhibitor

General Function

Rna-directed rna polymerase activity

Specific Function

RNA-dependent RNA polymerase which is responsible for replication and transcription of virus RNA segments. The transcription of viral mRNAs occurs by a unique mechanism called cap-snatching. 5' met...

Gene Name

PB1

Uniprot ID

P16502

Uniprot Name

RNA-directed RNA polymerase catalytic subunit

Molecular Weight

86534.5 Da

References

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
3. Bougie I, Bisaillon M: Initial binding of the broad spectrum antiviral nucleoside ribavirin to the hepatitis C virus RNA polymerase. J Biol Chem. 2003 Dec 26;278(52):52471-8. Epub 2003 Oct 16. [Article]

Enzymes

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Modulator

General Function

Broad specificity cytosolic 5'-nucleotidase that catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates (PubMed:10092873, PubMed:12907246, PubMed:1659319, PubMed:9371705). In addition, possesses a phosphotransferase activity by which it can transfer a phosphate from a donor nucleoside monophosphate to an acceptor nucleoside, preferably inosine, deoxyinosine and guanosine (PubMed:1659319, PubMed:9371705). Has the highest activities for IMP and GMP followed by dIMP, dGMP and XMP (PubMed:10092873, PubMed:12907246, PubMed:1659319, PubMed:9371705). Could also catalyze the transfer of phosphates from pyrimidine monophosphates but with lower efficiency (PubMed:1659319, PubMed:9371705). Through these activities regulates the purine nucleoside/nucleotide pools within the cell (PubMed:10092873, PubMed:12907246, PubMed:1659319, PubMed:9371705)

Specific Function

5'-nucleotidase activity

Gene Name

NT5C2

Uniprot ID

P49902

Uniprot Name

Cytosolic purine 5'-nucleotidase

Molecular Weight

64969.2 Da

References

1. Wu JZ, Larson G, Walker H, Shim JH, Hong Z: Phosphorylation of ribavirin and viramidine by adenosine kinase and cytosolic 5'-nucleotidase II: Implications for ribavirin metabolism in erythrocytes. Antimicrob Agents Chemother. 2005 Jun;49(6):2164-71. [Article]
2. Wallden K, Nordlund P: Structural basis for the allosteric regulation and substrate recognition of human cytosolic 5'-nucleotidase II. J Mol Biol. 2011 May 13;408(4):684-96. doi: 10.1016/j.jmb.2011.02.059. Epub 2011 Mar 17. [Article]

Kind

Protein

Organism

Humans

Pharmacological action

No

Actions

Activator

General Function

Catalyzes the phosphorylation of the purine nucleoside adenosine at the 5' position in an ATP-dependent manner. Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides

Specific Function

Adenosine kinase activity

Gene Name

ADK

Uniprot ID

P55263

Uniprot Name

Adenosine kinase

Molecular Weight

40545.075 Da

References

1. Wu JZ, Larson G, Walker H, Shim JH, Hong Z: Phosphorylation of ribavirin and viramidine by adenosine kinase and cytosolic 5'-nucleotidase II: Implications for ribavirin metabolism in erythrocytes. Antimicrob Agents Chemother. 2005 Jun;49(6):2164-71. [Article]
2. Kumarapperuma SC, Sun Y, Jeselnik M, Chung K, Parker WB, Jonsson CB, Arterburn JB: Structural effects on the phosphorylation of 3-substituted 1-beta-D-ribofuranosyl-1,2,4-triazoles by human adenosine kinase. Bioorg Med Chem Lett. 2007 Jun 1;17(11):3203-7. Epub 2007 Mar 12. [Article]

Transporters

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Substrate

General Function

Sodium-dependent, pyrimidine- and purine-selective (PubMed:11032837, PubMed:15861042, PubMed:16446384, PubMed:17140564, PubMed:21998139). Involved in the homeostasis of endogenous nucleosides (PubMed:11032837, PubMed:15861042). Exhibits the transport characteristics of the nucleoside transport system cib or N3 subtype (N3/cib) (with marked transport of both thymidine and inosine) (PubMed:11032837). Employs a 2:1 sodium/nucleoside ratio (PubMed:11032837). Transports uridine (PubMed:21795683). Also able to transport gemcitabine, 3'-azido-3'-deoxythymidine (AZT), ribavirin and 3-deazauridine (PubMed:11032837, PubMed:17140564)

Specific Function

Nucleoside

Gene Name

SLC28A3

Uniprot ID

Q9HAS3

Uniprot Name

Solute carrier family 28 member 3

Molecular Weight

76929.61 Da

References

1. Yamamoto T, Sugawara M, Kikukawa T, Miyauchi S, Yamaguchi M, Tero A, Takagi S, Nakagaki T: Kinetic study of anti-viral ribavirin uptake mediated by hCNT3 and hENT1 in Xenopus laevis oocytes. Biophys Chem. 2010 Mar;147(1-2):59-65. doi: 10.1016/j.bpc.2009.12.012. Epub 2010 Jan 6. [Article]

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Substrate

General Function

Uniporter involved in the facilitative transport of nucleosides and nucleobases, and contributes to maintaining their cellular homeostasis (PubMed:10722669, PubMed:10755314, PubMed:12527552, PubMed:14759222, PubMed:15037197, PubMed:17379602, PubMed:21795683, PubMed:26406980, PubMed:27995448, PubMed:35790189, PubMed:8986748). Functions as a Na(+)-independent transporter (PubMed:8986748). Involved in the transport of nucleosides such as adenosine, guanosine, inosine, uridine, thymidine and cytidine (PubMed:10722669, PubMed:10755314, PubMed:12527552, PubMed:14759222, PubMed:15037197, PubMed:17379602, PubMed:26406980, PubMed:8986748). Also transports purine nucleobases (hypoxanthine, adenine, guanine) and pyrimidine nucleobases (thymine, uracil) (PubMed:21795683, PubMed:27995448). Mediates basolateral nucleoside uptake into Sertoli cells, thereby regulating the transport of nucleosides in testis across the blood-testis barrier (By similarity). Regulates inosine levels in brown adipocytes tissues (BAT) and extracellular inosine levels, which controls BAT-dependent energy expenditure (PubMed:35790189)

Specific Function

Adenine transmembrane transporter activity

Gene Name

SLC29A1

Uniprot ID

Q99808

Uniprot Name

Equilibrative nucleoside transporter 1

Molecular Weight

50218.805 Da

References

1. Yamamoto T, Sugawara M, Kikukawa T, Miyauchi S, Yamaguchi M, Tero A, Takagi S, Nakagaki T: Kinetic study of anti-viral ribavirin uptake mediated by hCNT3 and hENT1 in Xenopus laevis oocytes. Biophys Chem. 2010 Mar;147(1-2):59-65. doi: 10.1016/j.bpc.2009.12.012. Epub 2010 Jan 6. [Article]
2. Fukuchi Y, Furihata T, Hashizume M, Iikura M, Chiba K: Characterization of ribavirin uptake systems in human hepatocytes. J Hepatol. 2010 Apr;52(4):486-92. doi: 10.1016/j.jhep.2010.01.011. Epub 2010 Feb 4. [Article]

Drug created at June 13, 2005 13:24 / Updated at September 19, 2024 06:09