Details of Disease

General Information of Disease (ID: DIS5VPYU)

Disease Name	Middle East Respiratory Syndrome (MERS)
Synonyms	camel flu; MERS
Disease Class	1D64: Middle East Respiratory Syndrome
Definition	A viral respiratory infection that is caused by the MERS coronavirus (MERS-CoV), which most often manifests with moderate to severe respiratory symptoms, including productive cough and shortness of breath, which can progress to pneumonia and acute respiratory distress syndrome.
Disease Hierarchy	DISGGAGJ: Respiratory disease DISPEEOC: Orthocoronavirinae infectious disease DISEM33Q: Infectious disease DIS5VPYU: Middle East Respiratory Syndrome (MERS)
ICD Code	ICD-11 ICD-11: 1D64
Disease Identifiers	MONDO ID MONDO_0100116 MESH ID D018352 UMLS CUI C3694279 MedGen ID 811327 Orphanet ID 576074 SNOMED CT ID 6.51E+11

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 26 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Acocantherin	DM7JT24	Approved	Small molecular drug	[1]
Amodiaquine	DME4RA8	Approved	Small molecular drug	[2]
Chloroquine	DMSI5CB	Approved	Small molecular drug	[1]
Chlorpromazine	DMBGZI3	Approved	Small molecular drug	[1]
Ciclosporin	DMAZJFX	Approved	NA	[3]
Dasatinib	DMJV2EK	Approved	Small molecular drug	[1]
Disulfiram	DMCL2OK	Approved	Small molecular drug	[3]
Everolimus	DM8X2EH	Approved	Small molecular drug	[1]
Fluphenazine	DMIT8LX	Approved	Small molecular drug	[4]
Gemcitabine	DMSE3I7	Approved	Small molecular drug	[2]
Imatinib	DM7RJXL	Approved	Small molecular drug	[1]
Loperamide	DMOJZQ9	Approved	Small molecular drug	[5]
Lopinavir	DMITQS0	Approved	Small molecular drug	[1]
Mefloquine	DMWT905	Approved	Small molecular drug	[2]
Mercaptopurine	DMTM2IK	Approved	Small molecular drug	[6]
Mycophenolate mofetil	DMPQAGE	Approved	Small molecular drug	[7]
Mycophenolic acid	DMRBMAU	Approved	NA	[8]
Nafamostat	DMU1XOD	Approved	Small molecular drug	[9]
Phenazopyridine	DM3MDOL	Approved	Small molecular drug	[7]
Promethazine	DM6I5GR	Approved	Small molecular drug	[2]
Remdesivir	DMBFZ6L	Approved	Small molecular drug	[10]
Ribavirin	DMEYLH9	Approved	Small molecular drug	[8]
Thiethylperazine	DMU3IET	Approved	Small molecular drug	[2]
Thioguanine	DM7NKEV	Approved	Small molecular drug	[6]
Trametinib	DM2JGQ3	Approved	Small molecular drug	[1]
Triflupromazine	DMKFQJP	Approved	Small molecular drug	[2]
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⏷ Show the Full List of 26 Drug(s)

This Disease is Treated as An Indication in 5 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Alisporivir	DM83EBP	Phase 3	Protein/peptide drug	[3]
Resveratrol	DM3RWXL	Phase 3	Small molecular drug	[11]
Selumetinib	DMC7W6R	Phase 3	Small molecular drug	[1]
INO-4700	DMYOGCF	Phase 2	Vaccine	[12]
Saracatinib	DMBLHGP	Phase 2	Small molecular drug	[13]
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This Disease is Treated as An Indication in 1 Drugs in Phase 2 Trial

Drug Name	Drug ID	Highest Status	Drug Type	REF
Camostat mesylate	DMVLXMG	Phase 2/3 Trial	Small molecular drug	[1]
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This Disease is Treated as An Indication in 7 Drugs in Phase 1 Trial

Drug Name	Drug ID	Highest Status	Drug Type	REF
BVRS-GamVac vaccine	DMKQBUR	Phase 1/2 Trial	Vaccine	[14]
BVRS-GamVac-Combi vaccine	DMF0L57	Phase 1/2 Trial	Vaccine	[15]
GLS-5300 vaccine	DMH7C14	Phase 1/2 Trial	Vaccine	[16]
MVA-MERS-S_DF-1 vaccine	DMO37IZ	Phase 1b Trial	Vaccine	[17]
ChAdOx1 MERS001 vaccine	DM10KLB	Phase 1 Trial	Vaccine	[18]
ChAdOx1 MERS002 vaccine	DMIYED0	Phase 1 Trial	Vaccine	[19]
Galidesivir	DMG9C4I	Phase 1 Trial	Small molecular drug	[1]
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⏷ Show the Full List of 7 Drug(s)

This Disease is Treated as An Indication in 4 Discontinued Drugs

Drug Name	Drug ID	Highest Status	Drug Type	REF
MVA-MERS-S vaccine	DM80HDZ	Discontinue in Phase 1 Trial	Vaccine	[20]
REGN 3048	DMW08TD	Discontinue in Phase 1 Trial	Monoclonal antibody	[21]
REGN 3051	DMLH28J	Discontinue in Phase 1 Trial	Monoclonal antibody	[21]
SAB-301	DMWCQSH	Discontinue in Phase 1 Trial	Polyclonal antibody	[22]
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This Disease is Treated as An Indication in 28 Preclinical Drugs

Drug Name	Drug ID	Highest Status	Drug Type	REF
Alpha-Helical lipopeptides FFS	DMATQB7	Preclinical	Protein/peptide drug	[23]
Alpha-Helical lipopeptides IIK	DMVSKQF	Preclinical	Protein/peptide drug	[23]
Alpha-Helical lipopeptides IIS	DM1MGBX	Preclinical	Protein/peptide drug	[23]
Alpha-Helical lipopeptides LLS	DM3WVM4	Preclinical	Protein/peptide drug	[23]
Dec-RVKR-CMK	DMJKQFT	Preclinical	Protein/peptide drug	[1]
E-64D	DMCVXBE	Preclinical	Small molecular drug	[1]
FA-613	DMTHLB8	Preclinical	Small molecular drug	[24]
GC376	DMR1CLY	Preclinical	Small molecular drug	[25]
GC813	DM7PBJC	Preclinical	Small molecular drug	[26]
GRL-001	DMVB1PD	Preclinical	Small molecular drug	[1]
HR1P peptide	DMNF9P5	Preclinical	Protein/peptide drug	[27]
HR2P peptide	DM6WC1Q	Preclinical	Protein/peptide drug	[27]
HR2P-M1 peptide	DMSR96X	Preclinical	Protein/peptide drug	[27]
HR2P-M2 peptide	DM7X4SV	Preclinical	Protein/peptide drug	[27]
K11777	DM86YBK	Preclinical	Small molecular drug	[1]
K22	DMDDG4Y	Preclinical	Small molecular drug	[28]
MERS-five-helix bundle	DMG5YRP	Preclinical	Protein/peptide drug	[29]
Peptide P21S10	DMMWQTI	Preclinical	Protein/peptide drug	[30]
PMID26048809-compound2	DMFNS7U	Preclinical	Small molecular drug	[1]
PMID26868298-compound-5705213	DMZMYU5	Preclinical	Small molecular drug	[1]
PMID26868298-compound-N3	DMQFUCD	Preclinical	Small molecular drug	[1]
PMID26911565-peptide-P9	DMUH012	Preclinical	Protein/peptide drug	[31]
PMID27240464-compound-3f	DMPC29W	Preclinical	Small molecular drug	[32]
PMID28216367-compound-6d	DMPWUFT	Preclinical	Small molecular drug	[33]
PMID30940566-compound-6	DMXCKL9	Preclinical	Small molecular drug	[34]
PMID31244113-compound-2c	DMZJWON	Preclinical	Small molecular drug	[35]
PMID31955138-compound-16	DM9LS0R	Preclinical	Small molecular drug	[36]
SSYA10-001	DM0NPIO	Preclinical	Small molecular drug	[1]
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⏷ Show the Full List of 28 Drug(s)

This Disease is Treated as An Indication in 14 Investigative Agents

Drug Name	Drug ID	Highest Status	Drug Type	REF
Amarylline	DML9W2V	Investigative	Small molecular drug	[7]
Emetine hydrochloride	DMN53QP	Investigative	Small molecular drug	[7]
Fusion peptide EK1	DMP3BZH	Investigative	Protein/peptide drug	[37]
MERS-CoV-SDNA vaccine	DMQ9HKM	Investigative	Vaccine	[1]
MERS-CoVS-containing nanoparticle vaccine	DMLQ9AL	Investigative	Vaccine	[1]
Monensin sodium	DMEFK3A	Investigative	Small molecular drug	[7]
Polyinosinic:polycytidylic acid	DM4VZCW	Investigative	Small molecular drug	[38]
Pyrvinium pamoate	DMI25N2	Investigative	Small molecular drug	[7]
Rapamycin	DM8GRJK	Investigative	Small molecular drug	[1]
rMERS-CoV-E vaccine	DMQAXKQ	Investigative	Vaccine	[1]
S(377588)-Fc vaccine	DMDXCF1	Investigative	Vaccine	[1]
Silvestrol	DM5JKNF	Investigative	Small molecular drug	[39]
VRP-S vaccine	DM2H0SR	Investigative	Vaccine	[1]
YS110 mAb clone	DMTURZ6	Investigative	Monoclonal antibody	[1]
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⏷ Show the Full List of 14 Drug(s)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ATP1A1	TTWK8D0	Limited	Biomarker	[41]
PDF	TT9SL3Q	Limited	Biomarker	[42]
PPP1CA	TTFLH0E	Limited	Genetic Variation	[43]
RNASEL	TT7V0K4	Limited	Biomarker	[44]
DEFB4A	TTIVY12	Strong	Biomarker	[45]
DPP4	TTDIGC1	Strong	Genetic Variation	[46]
ISG15	TTVOH3T	Strong	Biomarker	[47]
TMPRSS2	TT1GM2Z	Strong	Biomarker	[48]
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⏷ Show the Full List of 8 DTT(s)

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ASZ1	OTLM93UO	Limited	Genetic Variation	[49]
IFITM1	OTECO1G8	Limited	Genetic Variation	[50]
IFITM3	OT2QP8D3	Limited	Genetic Variation	[50]
SH2D3A	OTVJBSRC	Limited	Biomarker	[51]
SH2D3C	OTAGXO0N	Limited	Altered Expression	[52]
SH3BP5	OTOOEGUJ	Limited	Biomarker	[53]
SPECC1	OTPEML48	Limited	Biomarker	[43]
TMPRSS11A	OTB35677	Limited	Biomarker	[54]
TRIM25	OT35SG1R	Limited	Biomarker	[55]
CDSN	OTQW4HV6	Strong	Genetic Variation	[56]
SARS1	OTFKXQ1O	Strong	Biomarker	[57]
SARS2	OTU4T99W	Strong	Biomarker	[57]
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⏷ Show the Full List of 12 DOT(s)

References

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4	Testing of Middle East respiratory syndrome coronavirus replication inhibitors for the ability to block viral entry. Antimicrob Agents Chemother. 2015 Jan;59(1):742-4.
5	Screening of an FDA-approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture Antimicrob Agents Chemother. 2014 Aug;58(8):4875-84.
6	Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus. Antiviral Res. 2015 Mar;115:9-16.
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9	Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay Antimicrob Agents Chemother. 2016 Oct 21;60(11):6532-6539.
10	Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020 Jan 10;11(1):222.
11	Effective inhibition of MERS-CoV infection by resveratrol. BMC Infect Dis. 2017 Feb 13;17(1):144.
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13	Saracatinib Inhibits Middle East Respiratory Syndrome-Coronavirus Replication In Vitro. Viruses. 2018 May 24;10(6). pii: E283.
14	ClinicalTrials.gov (NCT04130594) Study of Safety and Immunogenicity of BVRS-GamVac. U.S. National Institutes of Health.
15	ClinicalTrials.gov (NCT04128059) Study of Safety and Immunogenicity of BVRS-GamVac-Combi. U.S. National Institutes of Health.
16	ClinicalTrials.gov (NCT03721718) Evaluate the Safety, Tolerability and Immunogenicity Study of GLS-5300 in Healthy Volunteers. U.S. National Institutes of Health.
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23	De Novo Design of -Helical Lipopeptides Targeting Viral Fusion Proteins: A Promising Strategy for Relatively Broad-Spectrum Antiviral Drug Discovery. J Med Chem. 2018 Oct 11;61(19):8734-8745.
24	Broad-spectrum inhibition of common respiratory RNA viruses by a pyrimidine synthesis inhibitor with involvement of the host antiviral response. J Gen Virol. 2017 May;98(5):946-954.
25	Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor. PLoS Pathog. 2016 Mar 30;12(3):e1005531.
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28	Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse coronaviruses including the middle East respiratory syndrome virus. PLoS Pathog. 2014 May 29;10(5):e1004166.
29	Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus. Viruses. 2017 Sep 14;9(9). pii: E255.
30	Discovery of Hydrocarbon-Stapled Short -Helical Peptides as Promising Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Fusion Inhibitors. J Med Chem. 2018 Mar 8;61(5):2018-2026.
31	A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses. Sci Rep. 2016 Feb 25;6:22008.
32	Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors. Bioorg Med Chem. 2016 Jul 1;24(13):3035-3042.
33	Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CLPro inhibitors. Antiviral Res. 2017 May;141:101-106.
34	Identification and Design of Novel Small Molecule Inhibitors Against MERS-CoV Papain-Like Protease via High-Throughput Screening and Molecular Modeling Bioorg Med Chem. 2019 May 15;27(10):1981-1989.
35	Design, Synthesis, and Anti-RNA Virus Activity of 6'-Fluorinated-Aristeromycin Analogues. J Med Chem. 2019 Jul 11;62(13):6346-6362.
36	Design, synthesis and molecular docking of novel triazole derivatives as potential CoV helicase inhibitors. Acta Pharm. 2020 Jun 1;70(2):145-159.
37	A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike. Sci Adv. 2019 Apr 10;5(4):eaav4580.
38	Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Infection, Immunological Response, and Vaccine Development. J Immunol Res. 2019 Apr 7;2019:6491738. doi: 10.1155/2019/6491738.
39	Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses. Antiviral Res. 2018 Feb;150:123-129.
40	ClinicalTrials.gov (NCT02845843) MERS-CoV Infection tReated With A Combination of Lopinavir /Ritonavir and Interferon Beta-1b
41	ATP1A1-mediated Src signaling inhibits coronavirus entry into host cells.J Virol. 2015 Apr;89(8):4434-48. doi: 10.1128/JVI.03274-14. Epub 2015 Feb 4.
42	Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus.mBio. 2017 Apr 4;8(2):e00373-17. doi: 10.1128/mBio.00373-17.
43	Prediction and biochemical analysis of putative cleavage sites of the 3C-like protease of Middle East respiratory syndrome coronavirus.Virus Res. 2015 Oct 2;208:56-65. doi: 10.1016/j.virusres.2015.05.018. Epub 2015 May 31.
44	Lineage A Betacoronavirus NS2 Proteins and the Homologous Torovirus Berne pp1a Carboxy-Terminal Domain Are Phosphodiesterases That Antagonize Activation of RNase L.J Virol. 2017 Feb 14;91(5):e02201-16. doi: 10.1128/JVI.02201-16. Print 2017 Mar 1.
45	Human -defensin 2 is involved in CCR2-mediated Nod2 signal transduction, leading to activation of the innate immune response in macrophages.Immunobiology. 2019 Jul;224(4):502-510. doi: 10.1016/j.imbio.2019.05.004. Epub 2019 May 18.
46	Sequential Emergence and Wide Spread of Neutralization Escape Middle East Respiratory Syndrome Coronavirus Mutants, South Korea, 2015.Emerg Infect Dis. 2019 Jun;25(6):1161-1168. doi: 10.3201/eid2506.181722. Epub 2019 Jun 17.
47	Decoupling deISGylating and deubiquitinating activities of the MERS virus papain-like protease.Antiviral Res. 2020 Feb;174:104661. doi: 10.1016/j.antiviral.2019.104661. Epub 2019 Nov 23.
48	TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection.J Virol. 2019 Mar 5;93(6):e01815-18. doi: 10.1128/JVI.01815-18. Print 2019 Mar 15.
49	MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis.mBio. 2017 Aug 22;8(4):e00665-17. doi: 10.1128/mBio.00665-17.
50	Identification of Residues Controlling Restriction versus Enhancing Activities of IFITM Proteins on Entry of Human Coronaviruses.J Virol. 2018 Feb 26;92(6):e01535-17. doi: 10.1128/JVI.01535-17. Print 2018 Mar 15.
51	The Endonucleolytic RNA Cleavage Function of nsp1 of Middle East Respiratory Syndrome Coronavirus Promotes the Production of Infectious Virus Particles in Specific Human Cell Lines.J Virol. 2018 Oct 12;92(21):e01157-18. doi: 10.1128/JVI.01157-18. Print 2018 Nov 1.
52	Expression and Cleavage of Middle East Respiratory Syndrome Coronavirus nsp3-4 Polyprotein Induce the Formation of Double-Membrane Vesicles That Mimic Those Associated with Coronaviral RNA Replication.mBio. 2017 Nov 21;8(6):e01658-17. doi: 10.1128/mBio.01658-17.
53	Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus antibody produced from transchromosomic cattle: a phase 1 randomised, double-blind, single-dose-escalation study.Lancet Infect Dis. 2018 Apr;18(4):410-418. doi: 10.1016/S1473-3099(18)30002-1. Epub 2018 Jan 9.
54	TMPRSS11A activates the influenza A virus hemagglutinin and the MERS coronavirus spike protein and is insensitive against blockade by HAI-1.J Biol Chem. 2018 Sep 7;293(36):13863-13873. doi: 10.1074/jbc.RA118.001273. Epub 2018 Jul 5.
55	The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination.J Virol. 2017 Mar 29;91(8):e02143-16. doi: 10.1128/JVI.02143-16. Print 2017 Apr 15.
56	Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization.J Virol. 2019 Jan 4;93(2):e01381-18. doi: 10.1128/JVI.01381-18. Print 2019 Jan 15.
57	Identification of 6'--fluoro-homoaristeromycin as a potent inhibitor of chikungunya virus replication.Eur J Med Chem. 2020 Feb 1;187:111956. doi: 10.1016/j.ejmech.2019.111956. Epub 2019 Dec 9.