Details of the Drug Combination

General Information of Drug Combination (ID: DCL4TNM)

• Drug Combination Name: Cobicistat + Darunavir
• Indication: Coronavirus Disease 2019 (COVID-19); Status: Phase 3 [1]
• Component Drugs:
  Cobicistat (DM6L4H2): Small molecular drug
  Darunavir (DMN3GCH): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cobicistat

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[2]

Cobicistat Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A (CYP3A)	TTIJQ3O	NOUNIPROTAC	Modulator	[2]

Cobicistat Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[6]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[7]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[7]

Indication(s) of Darunavir

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[3]
Human immunodeficiency virus-1 infection	1C62	Phase 3	[4]

Darunavir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Protease (HIV PR)	TT5FNQT	POL_HV1B1	Modulator	[8]

Darunavir Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[10]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[11]

Darunavir Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Human immunodeficiency virus infection	DC2HCN2	N. A.	Approved	[13]
AIDS-related Dementia Complex	DCGBGII	N. A.	Phase 4	[14]

References

• [1] ClinicalTrials.gov (NCT04252274) Efficacy and Safety of Darunavir and Cobicistat for Treatment of COVID-19
• [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: 7535).
• [3] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Drug interactions between hormonal contraceptives and antiretrovirals. AIDS. 2017 Apr 24;31(7):917-952.
• [6] Cobicistat versus ritonavir boosting and differences in the drug-drug interaction profiles with co-medications. J Antimicrob Chemother. 2016 Jul;71(7):1755-8.
• [7] Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity. Clin Pharmacol Ther. 2010 Mar;87(3):322-9.
• [8] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [9] Impact of drug transporters on cellular resistance towards saquinavir and darunavir. J Antimicrob Chemother. 2010 Nov;65(11):2319-28.
• [10] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [11] P-glycoprotein mediates efflux transport of darunavir in human intestinal Caco-2 and ABCB1 gene-transfected renal LLC-PK1 cell lines. Biol Pharm Bull. 2009 Sep;32(9):1588-93.
• [12] Drug interactions with new and investigational antiretrovirals. Clin Pharmacokinet. 2009;48(4):211-41.
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [14] ClinicalTrials.gov (NCT02503462) Effect of Cobicistat Versus Ritonavir Boosting on the Brain Permeation of Darunavir in HIV-infected Individuals