Details of the Drug Combination

General Information of Drug Combination (ID: DCUAY9A)

• Drug Combination Name: BOCEPREVIR + Raltegravir
• Indication: HIV Infections; Status: Phase 1 [1]
• Component Drugs:
  BOCEPREVIR (DMBSHMF): Small molecular drug
  Raltegravir (DMYURI6): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of BOCEPREVIR

Disease Entry	ICD 11	Status	REF
Hepatitis C virus infection	1E51.1	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[3]

BOCEPREVIR Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Hepatitis C virus Serine protease NS3/4A (HCV NS3/4A)	TTHC7JD	POLG_HCV1	Modulator	[5]
COVID-19 3C-like protease (3CLpro)	TT1D53B	R1AB_SARS2 (3264-3569)	Inhibitor	[3]

BOCEPREVIR Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]

BOCEPREVIR Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[8]

Indication(s) of Raltegravir

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[4]

Raltegravir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Integrase (HIV IN)	TT5FH9Y	POL_HV1B1	Modulator	[4]

Raltegravir Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[10]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[11]

References

• [1] ClinicalTrials.gov (NCT01288417) Pharmacokinetic Study of the HCV Protease Inhibitor Boceprevir and the HIV Integrase Inhibitor Raltegravir
• [2] 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: 7876).
• [3] Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. 2020. April 20. doi: https://doi.org/10.1101/2020.04.20.051581
• [4] 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
• [5] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [6] Drug interactions and protease inhibitors used in the treatment of hepatitis C: how to manage? Eur J Clin Pharmacol. 2014 Jul;70(7):775-89.
• [7] Pharmacokinetic evaluation of the interaction between hepatitis C virus protease inhibitor boceprevir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and pravastatin. Antimicrob Agents Chemother. 2013 Jun;57(6):2582-8.
• [8] Direct-acting antiviral agents for hepatitis C virus infection. Annu Rev Pharmacol Toxicol. 2013;53:427-49.
• [9] Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals. Antimicrob Agents Chemother. 2012 Jun;56(6):2959-66. doi: 10.1128/AAC.05424-11. Epub 2012 Feb 27.
• [10] Successful tacrolimus treatment following renal transplant in a HIV-infected patient with raltegravir previously treated with a protease inhibitor based regimen. Drug Metabol Drug Interact. 2011;26(3):139-41.
• [11] Exposure-related effects of atazanavir on the pharmacokinetics of raltegravir in HIV-1-infected patients. Ther Drug Monit. 2010 Dec;32(6):782-6.