Details of the Drug Combination

General Information of Drug Combination (ID: DCPFIBN)

• Drug Combination Name: Ribavirin + Lopinavir
• Indication: Middle East Respiratory Syndrome (MERS); Status: Investigative [1]
• Component Drugs:
  Ribavirin (DMEYLH9): Small molecular drug
  Lopinavir (DMITQS0): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

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	[5]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[1]

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	[9]
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	[1]
SARS-CoV RNA-directed RNA polymerase (RdRp)	TTKXI53	R1AB_CVHSA (4370-5301)	Inhibitor	[1]

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	[10]
Concentrative nucleoside transporter 2 (SLC28A2)	DT82KPY	S28A2_HUMAN	Substrate	[11]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3)	DT4YL5R	S28A3_HUMAN	Substrate	[12]
Equilibrative nucleoside transporter 1 (SLC29A1)	DTXD1TQ	S29A1_HUMAN	Substrate	[13]

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	[14]
Cytosolic 5'-nucleotidase II (NT5C2)	DE1DOKJ	5NTC_HUMAN	Metabolism	[15]

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	[16]
Protein arginine N-methyltransferase 3 (PRMT3)	OTH2KILE	ANM3_HUMAN	Decreases Expression	[8]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[17]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[18]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Decreases Expression	[19]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[20]
Erythropoietin (EPO)	OTZ90CN4	EPO_HUMAN	Increases Expression	[21]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[22]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Decreases Expression	[18]
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Decreases Expression	[18]
Intercellular adhesion molecule 1 (ICAM1)	OTTOIX77	ICAM1_HUMAN	Decreases Expression	[23]
Eukaryotic translation initiation factor 4E (EIF4E)	OTDAWNLA	IF4E_HUMAN	Decreases Expression	[8]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Decreases Expression	[16]
Myosin-6 (MYH6)	OT3YNCH1	MYH6_HUMAN	Decreases Expression	[22]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[22]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[16]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Decreases Expression	[18]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[17]
G1/S-specific cyclin-E1 (CCNE1)	OTLD7UID	CCNE1_HUMAN	Decreases Expression	[16]
Sodium-dependent serotonin transporter (SLC6A4)	OT6FGDLW	SC6A4_HUMAN	Increases Expression	[24]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[17]
Alpha-actinin-2 (ACTN2)	OT9FOLD7	ACTN2_HUMAN	Decreases Expression	[22]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Phosphorylation	[17]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[25]
Transcription factor GATA-4 (GATA4)	OTQHWAZG	GATA4_HUMAN	Decreases Expression	[22]
Troponin T, cardiac muscle (TNNT2)	OT80NN7R	TNNT2_HUMAN	Decreases Expression	[22]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10)	OT4PXBTA	TNF10_HUMAN	Decreases Response To Substance	[26]
Protein arginine N-methyltransferase 2 (PRMT2)	OT63JZCI	ANM2_HUMAN	Decreases Expression	[8]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Increases Expression	[18]
Insulin gene enhancer protein ISL-1 (ISL1)	OTVNVKAX	ISL1_HUMAN	Decreases Expression	[22]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Decreases Phosphorylation	[17]
Histone-arginine methyltransferase CARM1 (CARM1)	OT0IPRVR	CARM1_HUMAN	Decreases Expression	[8]
Protein arginine N-methyltransferase 6 (PRMT6)	OT5V3XIN	ANM6_HUMAN	Affects Expression	[8]
Protein arginine N-methyltransferase 1 (PRMT1)	OTN8GTXW	ANM1_HUMAN	Affects Expression	[8]
Protein arginine N-methyltransferase 8 (PRMT8)	OT3MRK62	ANM8_HUMAN	Decreases Expression	[8]
Protein arginine N-methyltransferase 7 (PRMT7)	OTE73PO1	ANM7_HUMAN	Decreases Expression	[16]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Increases ADR	[27]
Hepatocyte growth factor (HGF)	OTGHUA23	HGF_HUMAN	Increases ADR	[27]
Equilibrative nucleoside transporter 3 (SLC29A3)	OTGLX8XU	S29A3_HUMAN	Affects Transport	[28]
Haptoglobin (HP)	OTGUGAF9	HPT_HUMAN	Increases ADR	[27]
Equilibrative nucleoside transporter 1 (SLC29A1)	OTLOOZZS	S29A1_HUMAN	Increases Uptake	[29]
Interferon lambda-3 (IFNL3)	OTPIMGAU	IFNL3_HUMAN	Decreases Response	[30]
Inosine triphosphate pyrophosphatase (ITPA)	OTQ47WVR	ITPA_HUMAN	Increases Response To Substance	[31]

Indication(s) of Lopinavir

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[6]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[1]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[1]

Lopinavir Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial 23S ribosomal RNA (Bact 23S rRNA)	TTLFGBV	NOUNIPROTAC	Modulator	[33]
MERS-CoV 3C-like proteinase (3CLpro)	TTWOH4Q	R1AB_CVEMC (3248-3553)	Inhibitor	[1]
SARS-CoV 3C-like protease (3CLpro)	TTPZG3C	R1AB_CVHSA (3241-3546)	Inhibitor	[1]

Lopinavir Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[34]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[35]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[35]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[36]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[37]

Lopinavir Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[38]

Lopinavir Interacts with 14 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Activity	[39]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases Abundance	[40]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[41]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[42]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[42]
Prelamin-A/C (LMNA)	OT3SG7ZR	LMNA_HUMAN	Increases Farnesylation	[32]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[42]
Intercellular adhesion molecule 1 (ICAM1)	OTTOIX77	ICAM1_HUMAN	Increases Expression	[43]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Affects Phosphorylation	[44]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[43]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Increases Expression	[42]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[42]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Decreases Expression	[42]
Adiponectin (ADIPOQ)	OTNX23LE	ADIPO_HUMAN	Decreases Expression	[42]

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