Details of the Drug Combination

General Information of Drug Combination (ID: DC1BJAR)

• Drug Combination Name: Merimepodib + Remdesivir
• Indication: COVID-19; Status: Phase 2 [1]
• Component Drugs:
  Merimepodib (DM0HS92): Small molecular drug
  Remdesivir (DMBFZ6L): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Merimepodib

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Gastric adenocarcinoma	2B72	Phase 3	[2]
Hepatitis C virus infection	1E51.1	Phase 2b	[3]
Head and neck cancer	2D42	Phase 2	[2]
Hepatitis virus infection	1E50-1E51	Discontinued in Phase 2	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[5]

Merimepodib Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_HUMAN	Inhibitor	[9]
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1)	TTL7C8Q	IMDH1_HUMAN	Inhibitor	[10]
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[9]
HUMAN inosine-5'-monophosphate dehydrogenase 2 (IMPDH2)	TTTU6X1	IMDH2_HUMAN	Inhibitor	[5]

Indication(s) of Remdesivir

Disease Entry	ICD 11	Status	REF
Coronavirus Disease 2019 (COVID-19)	1D6Y	Approved	[6]
Ebola virus infection	1D60.0	Phase 1	[7]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[8]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[8]

Remdesivir Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
MERS-CoV RNA-directed RNA polymerase (RdRp)	TTOA6YT	R1AB_CVEMC (4378-5310)	Inhibitor	[8]
SARS-CoV RNA-directed RNA polymerase (RdRp)	TTKXI53	R1AB_CVHSA (4370-5301)	Inhibitor	[8]
COVID-19 RNA-directed RNA polymerase (RdRp)	TTV1095	R1AB_SARS2 (4393-5324)	Inhibitor	[11]
COVID-19 RNA-directed RNA polymerase (RdRp)	TTV1095	R1AB_SARS2 (4393-5324)	Inhibitor	[6]

Remdesivir Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[12]
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Increases Expression	[12]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Expression	[12]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[12]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Phosphorylation	[12]

References

• [1] ClinicalTrials.gov (NCT04410354) Study of Merimepodib in Combination With Remdesivir in Adult Patients With Advanced COVID-19
• [2] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 022059.
• [3] Merimepodib, Pegylated Interferon, and Ribavirin in Genotype 1 Chronic Hepatitis C Pegylated Interferon and Ribavirin Nonresponders. Hepatology. 2009 Dec;50(6):1719-26.
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008158)
• [5] The IMPDH inhibitor merimepodib suppresses SARS-CoV-2 replication in vitro. April 09, 2020. doi: https://doi.org/10.1101/2020.04.07.028589
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020 Jan 10;11(1):222.
• [9] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [10] VX-497: a novel, selective IMPDH inhibitor and immunosuppressive agent. J Pharm Sci. 2001 May;90(5):625-37.
• [11] Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271.
• [12] An in vitro study on anti-carcinogenic effect of remdesivir in human ovarian cancer cells via generation of reactive oxygen species. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221089257. doi: 10.1177/09603271221089257.