General Information of Drug Combination (ID: DCGE3TP)

Drug Combination Name
Ribavirin Interferon beta-1a
Indication
Disease Entry Status REF
Middle East Respiratory Syndrome (MERS) Investigative [1]
Component Drugs Ribavirin   DMEYLH9 Interferon beta-1a   DM1A6RV
Small molecular drug Protein/peptide drug

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Ribavirin
Disease Entry ICD 11 Status REF
Hepatitis C virus infection 1E51.1 Approved [2]
Respiratory syncytial virus infection 1C80 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [4]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [1]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [5]
Ribavirin Interacts with 5 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HUMAN inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) TT3GRLK IMDH1_HUMAN Inhibitor [4]
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) TTL7C8Q IMDH1_HUMAN Inhibitor [10]
HUMAN inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) TTTU6X1 IMDH2_HUMAN Inhibitor [4]
MERS-CoV RNA-directed RNA polymerase (RdRp) TTOA6YT R1AB_CVEMC (4378-5310) Inhibitor [5]
SARS-CoV RNA-directed RNA polymerase (RdRp) TTKXI53 R1AB_CVHSA (4370-5301) Inhibitor [5]
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Ribavirin Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [11]
Concentrative nucleoside transporter 2 (SLC28A2) DT82KPY S28A2_HUMAN Substrate [12]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3) DT4YL5R S28A3_HUMAN Substrate [13]
Equilibrative nucleoside transporter 1 (SLC29A1) DTXD1TQ S29A1_HUMAN Substrate [14]
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Ribavirin Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Purine nucleoside phosphorylase (PNP) DE2WSAL PNPH_HUMAN Metabolism [15]
Cytosolic 5'-nucleotidase II (NT5C2) DE1DOKJ 5NTC_HUMAN Metabolism [16]
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Ribavirin Interacts with 43 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Protein arginine N-methyltransferase 5 (PRMT5) OTF6IGJS ANM5_HUMAN Decreases Expression [17]
Protein arginine N-methyltransferase 3 (PRMT3) OTH2KILE ANM3_HUMAN Decreases Expression [9]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [18]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [19]
Interferon gamma (IFNG) OTXG9JM7 IFNG_HUMAN Decreases Expression [20]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [21]
Erythropoietin (EPO) OTZ90CN4 EPO_HUMAN Increases Expression [22]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [23]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [19]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Expression [19]
Intercellular adhesion molecule 1 (ICAM1) OTTOIX77 ICAM1_HUMAN Decreases Expression [24]
Eukaryotic translation initiation factor 4E (EIF4E) OTDAWNLA IF4E_HUMAN Decreases Expression [9]
Proliferating cell nuclear antigen (PCNA) OTHZ1RIA PCNA_HUMAN Decreases Expression [17]
Myosin-6 (MYH6) OT3YNCH1 MYH6_HUMAN Decreases Expression [23]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [23]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [17]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Decreases Expression [19]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [18]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Decreases Expression [17]
Sodium-dependent serotonin transporter (SLC6A4) OT6FGDLW SC6A4_HUMAN Increases Expression [25]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [18]
Alpha-actinin-2 (ACTN2) OT9FOLD7 ACTN2_HUMAN Decreases Expression [23]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [18]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [26]
Transcription factor GATA-4 (GATA4) OTQHWAZG GATA4_HUMAN Decreases Expression [23]
Troponin T, cardiac muscle (TNNT2) OT80NN7R TNNT2_HUMAN Decreases Expression [23]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10) OT4PXBTA TNF10_HUMAN Decreases Response To Substance [27]
Protein arginine N-methyltransferase 2 (PRMT2) OT63JZCI ANM2_HUMAN Decreases Expression [9]
Interleukin-2 (IL2) OTGI4NSA IL2_HUMAN Increases Expression [19]
Insulin gene enhancer protein ISL-1 (ISL1) OTVNVKAX ISL1_HUMAN Decreases Expression [23]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [18]
Histone-arginine methyltransferase CARM1 (CARM1) OT0IPRVR CARM1_HUMAN Decreases Expression [9]
Protein arginine N-methyltransferase 6 (PRMT6) OT5V3XIN ANM6_HUMAN Affects Expression [9]
Protein arginine N-methyltransferase 1 (PRMT1) OTN8GTXW ANM1_HUMAN Affects Expression [9]
Protein arginine N-methyltransferase 8 (PRMT8) OT3MRK62 ANM8_HUMAN Decreases Expression [9]
Protein arginine N-methyltransferase 7 (PRMT7) OTE73PO1 ANM7_HUMAN Decreases Expression [17]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases ADR [28]
Hepatocyte growth factor (HGF) OTGHUA23 HGF_HUMAN Increases ADR [28]
Equilibrative nucleoside transporter 3 (SLC29A3) OTGLX8XU S29A3_HUMAN Affects Transport [29]
Haptoglobin (HP) OTGUGAF9 HPT_HUMAN Increases ADR [28]
Equilibrative nucleoside transporter 1 (SLC29A1) OTLOOZZS S29A1_HUMAN Increases Uptake [30]
Interferon lambda-3 (IFNL3) OTPIMGAU IFNL3_HUMAN Decreases Response [31]
Inosine triphosphate pyrophosphatase (ITPA) OTQ47WVR ITPA_HUMAN Increases Response To Substance [32]
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⏷ Show the Full List of 43 DOT(s)
Indication(s) of Interferon beta-1a
Disease Entry ICD 11 Status REF
Multiple sclerosis 8A40 Approved [6]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [7]
Interferon beta-1a Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Interferon-beta (IFNB1) TT4TZ8J IFNB_HUMAN Modulator [33]
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References

1 SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016 Aug;14(8):523-34.
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Ribavirin FDA Label
4 Proteomics of SARS-CoV-2-infected Host Cells Reveals Therapy Targets. Nature. 2020 May 14. doi: 10.1038/s41586-020-2332-7.
5 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
6 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8339).
7 ClinicalTrials.gov (NCT04315948) Trial of Treatments for COVID-19 in Hospitalized Adults
8 Glutathione peroxidase, thioredoxin, and membrane protein changes in erythrocytes predict ribavirin-induced anemia. Clin Pharmacol Ther. 2005 Oct;78(4):422-32. doi: 10.1016/j.clpt.2005.07.002.
9 Ribavirin inhibits the growth and ascites formation of hepatocellular carcinoma through downregulation of type I CARM1 and type II PRMT5. Toxicol Appl Pharmacol. 2022 Jan 15;435:115829. doi: 10.1016/j.taap.2021.115829. Epub 2021 Dec 14.
10 Treating HCV with ribavirin analogues and ribavirin-like molecules. J Antimicrob Chemother. 2006 Jan;57(1):8-13.
11 Transport of levovirin prodrugs in the human intestinal Caco-2 cell line. J Pharm Sci. 2006 Jun;95(6):1318-25.
12 Identification and functional analysis of variants in the human concentrative nucleoside transporter 2, hCNT2 (SLC28A2) in Chinese, Malays and Indians. Pharmacogenet Genomics. 2007 Sep;17(9):783-6.
13 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.
14 Effects of dipyridamole coadministration on the pharmacokinetics of ribavirin in healthy volunteers. Drug Metab Pharmacokinet. 2013;28(5):406-10.
15 Functional analysis of purine nucleoside phosphorylase as a key enzyme in ribavirin metabolism. Drug Metab Pharmacokinet. 2014;29(2):211-4.
16 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.
17 Ribavirin inhibits colorectal cancer growth by downregulating PRMT5 expression and H3R8me2s and H4R3me2s accumulation. Toxicol Appl Pharmacol. 2021 Mar 15;415:115450. doi: 10.1016/j.taap.2021.115450. Epub 2021 Feb 9.
18 Ribavirin augments doxorubicin's efficacy in human hepatocellular carcinoma through inhibiting doxorubicin-induced eIF4E activation. J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22007. Epub 2017 Nov 7.
19 Ribavirin polarizes human T cell responses towards a Type 1 cytokine profile. J Hepatol. 1999 Mar;30(3):376-82. doi: 10.1016/s0168-8278(99)80093-2.
20 Direct evidence for immunomodulatory properties of ribavirin on T-cell reactivity to hepatitis C virus. Antiviral Res. 2007 Jul;75(1):36-42. doi: 10.1016/j.antiviral.2006.11.008. Epub 2006 Dec 13.
21 Profiling the immunotoxicity of chemicals based on in vitro evaluation by a combination of the Multi-ImmunoTox assay and the IL-8 Luc assay. Arch Toxicol. 2018 Jun;92(6):2043-2054. doi: 10.1007/s00204-018-2199-7. Epub 2018 Mar 29.
22 Normal erythropoietin response in chronic hepatitis C patients with ribavirin-induced anaemia. Antivir Ther. 2003 Feb;8(1):57-63.
23 Inhibition of cardiomyocyte differentiation of human induced pluripotent stem cells by Ribavirin: Implication for its cardiac developmental toxicity. Toxicology. 2020 Apr 15;435:152422. doi: 10.1016/j.tox.2020.152422. Epub 2020 Feb 26.
24 Correlation of sICAM-1 and sVCAM-1 level with biochemical, histological and viral findings in chronic hepatitis C after interferon-alpha + ribavirin therapy. Rom J Gastroenterol. 2003 Jun;12(2):91-5.
25 Serotonin transporter mRNA expression is decreased by lamivudine and ribavirin and increased by interferon in immune cells. Scand J Immunol. 2006 Feb;63(2):106-15. doi: 10.1111/j.1365-3083.2005.01715.x.
26 Ribavirin and alpha interferon enhance death receptor-mediated apoptosis and caspase activation in human hepatoma cells. Antimicrob Agents Chemother. 2003 Jun;47(6):1912-21. doi: 10.1128/AAC.47.6.1912-1921.2003.
27 Two distinct phases of virus-induced nuclear factor kappa B regulation enhance tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in virus-infected cells. J Biol Chem. 2003 May 16;278(20):18092-100. doi: 10.1074/jbc.M300265200. Epub 2003 Mar 13.
28 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
29 Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G910-22. doi: 10.1152/ajpgi.90672.2008. Epub 2009 Jan 22.
30 Characterization of ribavirin uptake systems in human hepatocytes. J Hepatol. 2010 Apr;52(4):486-92.
31 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and PEG interferon--based regimens. Clin Pharmacol Ther. 2014 Feb;95(2):141-6. doi: 10.1038/clpt.2013.203. Epub 2013 Oct 4.
32 ITPA polymorphism affects ribavirin-induced anemia and outcomes of therapy--a genome-wide study of Japanese HCV virus patients. Gastroenterology. 2010 Oct;139(4):1190-7. doi: 10.1053/j.gastro.2010.06.071. Epub 2010 Jul 14.
33 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.