General
Preferred name
RIBAVIRIN
Synonyms
ICN-1229 ()
NSC-163039 ()
Tribavirin ()
RTCA ()
1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide ()
Ribavirin (ICN-1229) ()
NSC-163039, RTCA, Tribavirin ()
Ribavirin mylan ()
Cotronak ()
Ribasphere ()
Rebetol ()
Ribapak ()
Ribavirin teva ()
Viramid ()
SCH 18908 ()
Ribavirin biopartners ()
Virazid ()
Ribofluranosyl Carboxamide ()
Ribavarin ()
Copegus ()
Virazole ()
SCH-18908 ()
Ribavirin-13C5 ()
P&D ID
PD000797
CAS
36791-04-5
252269-50-4
1646818-35-0
Tags
prodrug
natural product
drug
available
Approved by
PMDA
FDA
First approval
1985
Drug Status
approved
withdrawn
Drug indication
Antiviral
Hepatitis C virus infection
Severe acute respiratory syndrome (SARS)
Middle East Respiratory Syndrome (MERS)
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
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 [A19644].; ; 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.
DESCRIPTION Inhibits inosine-5'-monophosphate dehydrogenase 1 and RNA and also inhibits hepatitis C virus RNA-dependent RNA polymerase (NS5B). (GtoPdb)
MOA 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 [A19645]. 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 [A19645].; ; 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 [A19645].; ; 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 [A19645]. 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 [A19644].
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 [A19644]. ; 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.
DESCRIPTION Inhibits EGFR activation; also induces apoptosis (Tocris Bioactive Compound Library)
DESCRIPTION Antiviral guanosine analog; blocks eIF4E activity (Tocriscreen Plus)
DESCRIPTION Antiviral agent; its metabolite, ribavirin 5'-phosphate, is an inhibitor of inosine monophosphate (IMP) dehydrogenase (LOPAC library)
Cell lines
20
Organisms
37
Compound Sets
31
AdooQ Bioactive Compound Library
A10788
Cayman Chemical Bioactives
16757
34882
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
CHEMBL1643
ChEMBL Drugs
CHEMBL1643
Concise Guide to Pharmacology 2017/18
6842
Concise Guide to Pharmacology 2019/20
6842
Concise Guide to Pharmacology 2021/22
6842
Concise Guide to Pharmacology 2023/24
6842
Drug Repurposing Hub
DrugBank
DB00811
DrugBank Approved Drugs
DB00811
DrugCentral
2373
DrugCentral Approved Drugs
2373
DrugMAP
DM2A1DP
DMEYLH9
DrugMAP Approved Drugs
DMEYLH9
Enamine BioReference Compounds
Guide to Pharmacology
6842
LINCS compound set
10516-999
LOPAC library
NCATS Inxight Approved Drugs
49717AWG6K
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
Ribavirin(Copegus)
TargetMol Bioactive Compound Library
T0684
The Spectrum Collection
Tocris Bioactive Compound Library
4501
Tocriscreen Plus
4501
Withdrawn 2.0
w263
External IDs
53
Properties
(calculated by RDKit )
Molecular Weight
244.08
Hydrogen Bond Acceptors
8
Hydrogen Bond Donors
4
Rotatable Bonds
3
Ring Count
2
Aromatic Ring Count
1
cLogP
-3.01
TPSA
143.72
Fraction CSP3
0.62
Chiral centers
4.0
Largest ring
5.0
QED
0.44
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
Cell Biology
Selectivity
IMP dehydrogenase
MOA
viral RNA polymerase inhibitor
Hepatitis C virus inhibitor
Inosine 5'-Monophosphate Dehydrogenase (IMPDH) Inhibitors
Antiviral
Target
Inosine-5'-monophosphate dehydrogenase 1
RNA
Hepatitis C virus NS5B RNA-dependent RNA polymerase
ADK
IMPDH1
RNA polymerase
ADK, ENPP1, IMPDH1, IMPDH2, NT5C2
Pathway
DNA Damage/DNA Repair
Metabolism
Neuroscience
Primary Target
Protein-synthesizing GTPases
Member status
member
Indication
hepatitis C
ATC
J05AB04
Toxicity type
respiratory
Therapeutic Class
Antiviral Agents
Source data