Details of the Drug Combination

General Information of Drug Combination (ID: DC5HNLI)

Drug Combination Name
Azithromycin Hydroxychloroquine
Indication
Disease Entry Status REF
Coronavirus Disease 2019 (COVID-19) Phase 3 [1]
Component Drugs Azithromycin   DMS6UOE Hydroxychloroquine   DMSIVND
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Azithromycin
Disease Entry ICD 11 Status REF
Acute gonococcal cervicitis N.A. Approved [2]
Bronchitis CA20 Approved [3]
Chancroid N.A. Approved [2]
Mycoplasma pneumoniae pneumonia N.A. Approved [2]
Staphylococcus aureus infection N.A. Approved [2]
Streptococcal pneumonia N.A. Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [4]
Pneumonia caused by chlamydia N.A. Investigative [2]
Indication(s) of Hydroxychloroquine
Disease Entry ICD 11 Status REF
Chronic renal failure GB61.Z Approved [5]
Malaria 1F40-1F45 Approved [6]
Plasmodium falciparum malaria 1F40 Approved [5]
Plasmodium malariae malaria N.A. Approved [5]
Plasmodium ovale malaria N.A. Approved [5]
Systemic lupus erythematosus 4A40.0 Approved [5]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [7]
Colon cancer 2B90.Z Investigative [5]
Hydroxychloroquine Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HUMAN pH-dependent viral fusion/replication (pH-DVF/R) TTD16BI N.A. Inhibitor [8]
HUMAN glycosylation of host receptor (GHR) TTZGK1R N.A. Inhibitor [8]
Toll-like receptor 7 (TLR7) TTRJ1K4 TLR7_HUMAN Antagonist [9]
HUMAN toll-like receptor 7/9 signalling pathway (TLR7/9 pathway) TT3A1EZ N.A. Inhibitor [10]
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Hydroxychloroquine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [11]
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Hydroxychloroquine 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]
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Hydroxychloroquine Interacts with 30 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Decreases Activity [13]
Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) OTPGHZB9 IFIT3_HUMAN Increases Expression [14]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Decreases Expression [15]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1) OTY9R6FZ ERN1_HUMAN Increases Expression [14]
Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) OT4TMERS NFAC1_HUMAN Affects Expression [16]
Claudin-1 (CLDN1) OT27KV99 CLD1_HUMAN Increases Expression [17]
Interferon beta (IFNB1) OTYQGUB5 IFNB_HUMAN Increases Expression [14]
C-X-C motif chemokine 10 (CXCL10) OTTLQ6S0 CXL10_HUMAN Increases Expression [14]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Affects Expression [18]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL) OTG7J4BP PPBT_HUMAN Affects Expression [18]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Phosphorylation [14]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Affects Localization [19]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Expression [20]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [21]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [21]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Degradation [14]
CD40 ligand (CD40LG) OT75Z6A6 CD40L_HUMAN Decreases Expression [16]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [15]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Increases Expression [14]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Activity [19]
TNF receptor-associated factor 3 (TRAF3) OT5TQBGV TRAF3_HUMAN Increases Expression [14]
Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2) OTK5T6HZ NFAC2_HUMAN Affects Localization [16]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Increases Expression [22]
Interferon regulatory factor 3 (IRF3) OT81U8ME IRF3_HUMAN Increases Phosphorylation [14]
Occludin (OCLN) OTSUTVWL OCLN_HUMAN Increases Expression [17]
Mitochondrial antiviral-signaling protein (MAVS) OTTQ0J64 MAVS_HUMAN Increases Expression [14]
S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (RSAD2) OTCA9WCM RSAD2_HUMAN Increases Expression [14]
Interferon-induced helicase C domain-containing protein 1 (IFIH1) OTZA2AHA IFIH1_HUMAN Increases Expression [14]
Toll-like receptor 9 (TLR9) OTFZ45HX TLR9_HUMAN Decreases Expression [23]
7-dehydrocholesterol reductase (DHCR7) OTLILBUI DHCR7_HUMAN Affects Expression [18]
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⏷ Show the Full List of 30 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
COVID19 DC8Y9J6 N. A. Phase 3 [24]
Coronavirus Disease 2019 (COVID-19) DCHHDRF N. A. Phase 3 [25]
Virus Diseases DC6CLQX N. A. Phase 2 [26]
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References

1 ClinicalTrials.gov (NCT04321278) Safety and Efficacy of Hydroxychloroquine Associated With Azithromycin in SARS-CoV2 Virus (Coalition Covid-19 Brasil II). U.S. National Institutes of Health.
2 Azithromycin FDA Label
3 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 065511.
4 ClinicalTrials.gov (NCT04332107) Azithromycin for COVID-19 Treatment in Outpatients Nationwide. U.S. National Institutes of Health.
5 Hydroxychloroquine FDA Label
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: 7198).
7 ClinicalTrials.gov (NCT04341727) Hydroxychloroquine,Hydroxychloroquine,Azithromycin in the Treatment of SARS CoV-2 Infection (WU352). U.S. National Institutes of Health.
8 Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271.
9 TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007 Dec;6(4):223-35.
10 Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020 Mar;16(3):155-166.
11 MDR-ABC transporters: biomarkers in rheumatoid arthritis. Clin Exp Rheumatol. 2013 Sep-Oct;31(5):779-87.
12 Hydroxychloroquine: a physiologically-based pharmacokinetic model in the context of cancer-related autophagy modulation. J Pharmacol Exp Ther. 2018 Jun;365(3):447-459.
13 Somer M, Kallio J, Pesonen U, Pyykko K, Huupponen R, Scheinin M "Influence of hydroxychloroquine on the bioavailability of oral metoprolol." Br J Clin Pharmacol 49 (2000): 549-54. [PMID: 10848718]
14 Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery. J Interferon Cytokine Res. 2015 Mar;35(3):143-56. doi: 10.1089/jir.2014.0038. Epub 2014 Oct 16.
15 Hydroxychloroquine potentiates Fas-mediated apoptosis of rheumatoid synoviocytes. Clin Exp Immunol. 2006 Jun;144(3):503-11. doi: 10.1111/j.1365-2249.2006.03070.x.
16 Hydroxychloroquine inhibits CD154 expression in CD4(+) T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther. 2017 Aug 9;19(1):183. doi: 10.1186/s13075-017-1393-y.
17 Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability. J Biochem Mol Toxicol. 2015 Jul;29(7):299-304. doi: 10.1002/jbt.21696. Epub 2015 Mar 9.
18 Hydroxychloroquine decreases human MSC-derived osteoblast differentiation and mineralization in vitro. J Cell Mol Med. 2018 Feb;22(2):873-882. doi: 10.1111/jcmm.13373. Epub 2017 Oct 3.
19 Mitochondrial membrane permeabilization is a critical step of lysosome-initiated apoptosis induced by hydroxychloroquine. Oncogene. 2003 Jun 19;22(25):3927-36. doi: 10.1038/sj.onc.1206622.
20 Attenuation of chloroquine and hydroxychloroquine on the invasive potential of bladder cancer through targeting matrix metalloproteinase 2 expression. Environ Toxicol. 2021 Nov;36(11):2138-2145. doi: 10.1002/tox.23328. Epub 2021 Jul 19.
21 Reactive oxygen species mediate chloroquine-induced expression of chemokines by human astroglial cells. Glia. 2004 Jul;47(1):9-20. doi: 10.1002/glia.20017.
22 d-galactose induces premature senescence of lens epithelial cells by disturbing autophagy flux and mitochondrial functions. Toxicol Lett. 2018 Jun 1;289:99-106. doi: 10.1016/j.toxlet.2018.02.001. Epub 2018 Feb 6.
23 Antagonist-mediated down-regulation of Toll-like receptors increases the prevalence of human papillomavirus infection in systemic lupus erythematosus. Arthritis Res Ther. 2012 Apr 18;14(2):R80. doi: 10.1186/ar3803.
24 ClinicalTrials.gov (NCT04328272) Effectiveness of Hydroxychloroquine in Covid-19 Patients
25 ClinicalTrials.gov (NCT04371406) Efficacy of Azithromycin-associated Hydroxychloroquine Therapy Given in General Practice in Early-stage Disease in COVID-19 Patients. U.S. National Institutes of Health.
26 ClinicalTrials.gov (NCT04322396) Proactive Protection With Azithromycin and hydroxyChloroquine in Hospitalized Patients With COVID-19