Details of Disease

General Information of Disease (ID: DISYW14W)

Disease Name	Severe acute respiratory syndrome (SARS)
Synonyms	SARS; acute respiratory coronavirus infection; SARS-CoV infection; SARS coronavirus caused disease or disorder; SARS coronavirus disease or disorder; SARS coronavirus infectious disease
Disease Class	1D65: Severe acute respiratory syndrome
Definition	A viral respiratory infection caused by the SARS coronavirus. It is transmitted through close person-to-person contact. It is manifested with high fever, headache, dry cough and myalgias. It may progress to pneumonia and cause death.
Disease Hierarchy	DISGGAGJ: Respiratory disease DISBV50J: Acute disease DISPEEOC: Orthocoronavirinae infectious disease DISEM33Q: Infectious disease DISYW14W: Severe acute respiratory syndrome (SARS)
ICD Code	ICD-11 ICD-11: 1D65
Disease Identifiers	MONDO ID MONDO_0005091 MESH ID D045169 UMLS CUI C1175175 MedGen ID 262817 Orphanet ID 140896 SNOMED CT ID 398447004

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 23 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Amodiaquine	DME4RA8	Approved	Small molecular drug	[1]
Chloroquine	DMSI5CB	Approved	Small molecular drug	[2]
Chlorpromazine	DMBGZI3	Approved	Small molecular drug	[3]
Ciclosporin	DMAZJFX	Approved	NA	[2]
Dasatinib	DMJV2EK	Approved	Small molecular drug	[3]
Disulfiram	DMCL2OK	Approved	Small molecular drug	[2]
Everolimus	DM8X2EH	Approved	Small molecular drug	[3]
Fluphenazine	DMIT8LX	Approved	Small molecular drug	[1]
Gemcitabine	DMSE3I7	Approved	Small molecular drug	[1]
Imatinib	DM7RJXL	Approved	Small molecular drug	[3]
Loperamide	DMOJZQ9	Approved	Small molecular drug	[4]
Lopinavir	DMITQS0	Approved	Small molecular drug	[3]
Mefloquine	DMWT905	Approved	Small molecular drug	[1]
Mercaptopurine	DMTM2IK	Approved	Small molecular drug	[5]
Promethazine	DM6I5GR	Approved	Small molecular drug	[2]
Remdesivir	DMBFZ6L	Approved	Small molecular drug	[6]
Ribavirin	DMEYLH9	Approved	Small molecular drug	[3]
Rimantadine	DM5DWMU	Approved	Small molecular drug	[7]
Streptokinase	DM5JQ0D	Approved	Small molecular drug	[8]
Thioguanine	DM7NKEV	Approved	Small molecular drug	[5]
Trametinib	DM2JGQ3	Approved	Small molecular drug	[3]
Triflupromazine	DMKFQJP	Approved	Small molecular drug	[1]
Zanamivir	DMFMBZ4	Approved	Small molecular drug	[9]
------------------------------------------------------------------------------------


⏷ Show the Full List of 23 Drug(s)

This Disease is Treated as An Indication in 2 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Alisporivir	DM83EBP	Phase 3	Protein/peptide drug	[3]
Selumetinib	DMC7W6R	Phase 3	Small molecular drug	[3]
------------------------------------------------------------------------------------

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	[3]
------------------------------------------------------------------------------------

This Disease is Treated as An Indication in 1 Drugs in Phase 1 Trial

Drug Name	Drug ID	Highest Status	Drug Type	REF
Galidesivir	DMG9C4I	Phase 1 Trial	Small molecular drug	[3]
------------------------------------------------------------------------------------

This Disease is Treated as An Indication in 4 Discontinued Drugs

Drug Name	Drug ID	Highest Status	Drug Type	REF
Alferon LDO	DML2P1A	Discontinue in Phase 2 Trial	Protein/peptide drug	[10]
Recombinant S protein SARS vaccine	DMQDMP0	Discontinue in Phase 1 Trial	Vaccine	[11]
SARS-CoV vaccine	DM52AQH	Discontinue in Phase 1 Trial	Vaccine	[12]
VRC-SRSDNA015-00-VP vaccine	DMBJLH6	Discontinue in Phase 1 Trial	Vaccine	[13]
------------------------------------------------------------------------------------

This Disease is Treated as An Indication in 19 Preclinical Drugs

Drug Name	Drug ID	Highest Status	Drug Type	REF
E-64D	DMCVXBE	Preclinical	Small molecular drug	[3]
FA-613	DMTHLB8	Preclinical	Small molecular drug	[14]
GC376	DMR1CLY	Preclinical	Small molecular drug	[15]
Griffithsin	DMNZA4L	Preclinical	Protein/peptide drug	[3]
GRL-001	DMVB1PD	Preclinical	Small molecular drug	[3]
Hexamethylene amiloride	DMLZ5TQ	Preclinical	Small molecular drug	[3]
K11777	DM86YBK	Preclinical	Small molecular drug	[3]
K22	DMDDG4Y	Preclinical	Small molecular drug	[16]
Phenylisoserine derivatives SK80	DM16W8F	Preclinical	Small molecular drug	[17]
PMID21925774-compound-5e	DM94ZOI	Preclinical	Small molecular drug	[18]
PMID26868298-compound-5705213	DMZMYU5	Preclinical	Small molecular drug	[3]
PMID26868298-compound-N3	DMQFUCD	Preclinical	Small molecular drug	[3]
PMID26911565-peptide-P9	DMUH012	Preclinical	Protein/peptide drug	[19]
PMID27240464-compound-3f	DMPC29W	Preclinical	Small molecular drug	[20]
PMID28216367-compound-6d	DMPWUFT	Preclinical	Small molecular drug	[21]
PMID28624700-compound-3-31	DMYNCWK	Preclinical	Small molecular drug	[22]
PMID30784880-compound-6-5	DMVB0P3	Preclinical	Small molecular drug	[23]
PMID31244113-compound-2c	DMZJWON	Preclinical	Small molecular drug	[24]
SSYA10-001	DM0NPIO	Preclinical	Small molecular drug	[3]
------------------------------------------------------------------------------------


⏷ Show the Full List of 19 Drug(s)

This Disease is Treated as An Indication in 7 Investigative Agents

Drug Name	Drug ID	Highest Status	Drug Type	REF
4E2Rcat	DMD6ROZ	Investigative	Small molecular drug	[25]
Amantidine	DMMT5Q4	Investigative	Small molecular drug	[26]
Fusion peptide EK1	DMP3BZH	Investigative	Protein/peptide drug	[27]
GRL-0667	DML09OS	Investigative	Small molecular drug	[28]
N-(2-aminoethyl)-1-aziridine-ethanamine	DMRK4FA	Investigative	Small molecular drug	[3]
PMID20527968-compound-6577871	DMI30V7	Investigative	Small molecular drug	[28]
Rapamycin	DM8GRJK	Investigative	Small molecular drug	[3]
------------------------------------------------------------------------------------


⏷ Show the Full List of 7 Drug(s)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 13 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CXCL1	TTLK1RW	Limited	Biomarker	[29]
FCER2	TTCH6MU	Limited	Biomarker	[30]
FGL2	TTYBS89	Limited	Altered Expression	[31]
GOT1	TTU507L	Limited	Biomarker	[32]
MASP2	TTR01E9	Limited	Genetic Variation	[33]
PI4KB	TTNPL3B	Limited	Biomarker	[34]
RNASEL	TT7V0K4	Limited	Biomarker	[35]
TMPRSS11D	TTWHYC8	Limited	Biomarker	[36]
TMPRSS2	TT1GM2Z	moderate	Biomarker	[37]
BST2	TT90BJT	Strong	Biomarker	[38]
CD209	TTBXIM9	Strong	Biomarker	[39]
CXCL10	TTQOVYA	Strong	Biomarker	[40]
MBL2	TTMQDZ5	Strong	Genetic Variation	[41]
------------------------------------------------------------------------------------


⏷ Show the Full List of 13 DTT(s)

This Disease Is Related to 19 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ACRV1	OTUTG7PL	Limited	Biomarker	[42]
BCAR3	OTPJ17M8	Limited	Biomarker	[43]
CTRL	OTB6NA5O	Limited	Biomarker	[44]
CXCL6	OTFTCQ4O	Limited	Biomarker	[29]
GNL1	OTWTVIVM	Limited	Biomarker	[45]
ICAM3	OTTZ5A5D	Limited	Biomarker	[30]
IL12RB1	OTM1IJO2	Limited	Genetic Variation	[46]
NFIC	OTLMCUIB	Limited	Genetic Variation	[47]
RNASE2	OT8Z4FNE	Limited	Altered Expression	[48]
RTN2	OTTZ5FW0	Limited	Biomarker	[43]
TRIM25	OT35SG1R	Limited	Biomarker	[49]
CLEC4M	OT2WUIIP	moderate	Genetic Variation	[50]
CDSN	OTQW4HV6	Strong	Biomarker	[51]
CKLF	OTHLPHA0	Strong	Biomarker	[52]
MX1	OT6X8G5T	Strong	Genetic Variation	[53]
MYOM2	OTD2UOXW	Strong	Biomarker	[54]
OAS1	OT8ZLOCY	Strong	Genetic Variation	[55]
SH2D3A	OTVJBSRC	Strong	Biomarker	[56]
SPECC1	OTPEML48	Strong	Biomarker	[43]
------------------------------------------------------------------------------------


⏷ Show the Full List of 19 DOT(s)

References

1	Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93.
2	Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020 Mar;19(3):149-150.
3	Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
4	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.
5	Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus. Antiviral Res. 2015 Mar;115:9-16.
6	Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020 Jan 10;11(1):222.
7	In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol. 2004 Sep;31(1):69-75. doi: 10.1016/j.jcv.2004.03.003.
8	ClinicalTrials.gov (NCT03465085) Streptokinase Versus Unfractionated Heparin Nebulization in Severe ARDS. U.S. National Institutes of Health.
9	Inhibition of SARS coronavirus infection in vitro with clinically approved antiviral drugs. Emerg Infect Dis. 2004 Apr;10(4):581-6. doi: 10.3201/eid1004.030458.
10	ClinicalTrials.gov (NCT00215826) Study of Alferon LDO (Low Dose Oral) in Normal Volunteers. U.S. National Institutes of Health.
11	ClinicalTrials.gov (NCT01376765) Phase I Dose Escalation SARS-CoV Recombinant S Protein, With and Without Adjuvant, Vaccine Study. U.S. National Institutes of Health.
12	ClinicalTrials.gov (NCT00533741) SARS Coronavirus Vaccine (SARS-CoV). U.S. National Institutes of Health.
13	ClinicalTrials.gov (NCT00099463) Phase I Study of a Vaccine for Severe Acute Respiratory Syndrome (SARS). U.S. National Institutes of Health.
14	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.
15	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.
16	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.
17	Synthesis and Evaluation of Phenylisoserine Derivatives for the SARS-CoV 3CL Protease Inhibitor. Bioorg Med Chem Lett. 2017 Jun 15;27(12):2746-2751.
18	2,6-Bis-arylmethyloxy-5-hydroxychromones With Antiviral Activity Against Both Hepatitis C Virus (HCV) and SARS-associated Coronavirus (SCV) Eur J Med Chem. 2011 Nov;46(11):5698-704.
19	A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses. Sci Rep. 2016 Feb 25;6:22008.
20	Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors. Bioorg Med Chem. 2016 Jul 1;24(13):3035-3042.
21	Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CLPro inhibitors. Antiviral Res. 2017 May;141:101-106.
22	Discovery of Unsymmetrical Aromatic Disulfides as Novel Inhibitors of SARS-CoV Main Protease: Chemical Synthesis, Biological Evaluation, Molecular Docking and 3D-QSAR Study Eur J Med Chem. 2017 Sep 8;137:450-461.
23	Chemical synthesis, crystal structure, versatile evaluation of their biological activities and molecular simulations of novel pyrithiobac derivatives. Eur J Med Chem. 2019 Apr 1;167:472-484.
24	Design, Synthesis, and Anti-RNA Virus Activity of 6'-Fluorinated-Aristeromycin Analogues. J Med Chem. 2019 Jul 11;62(13):6346-6362.
25	Blocking eIF4E-eIF4G interaction as a strategy to impair coronavirus replication. J Virol. 2011 Jul;85(13):6381-9.
26	Coronavirus envelope protein: current knowledge. Virol J. 2019 May 27;16(1):69.
27	A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike. Sci Adv. 2019 Apr 10;5(4):eaav4580.
28	Severe acute respiratory syndrome coronavirus papain-like novel protease inhibitors: design, synthesis, protein-ligand X-ray structure and biologic... J Med Chem. 2010 Jul 8;53(13):4968-79.
29	Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response.J Gen Virol. 2009 Dec;90(Pt 12):2956-2964. doi: 10.1099/vir.0.014282-0. Epub 2009 Sep 9.
30	Association of ICAM3 genetic variant with severe acute respiratory syndrome.J Infect Dis. 2007 Jul 15;196(2):271-80. doi: 10.1086/518892. Epub 2007 Jun 5.
31	Severe acute respiratory syndrome coronavirus nucleocapsid protein does not modulate transcription of the human FGL2 gene.J Gen Virol. 2009 Sep;90(Pt 9):2107-13. doi: 10.1099/vir.0.009209-0. Epub 2009 May 7.
32	Sequential changes of serum aminotransferase levels in patients with severe acute respiratory syndrome.Am J Trop Med Hyg. 2004 Aug;71(2):125-8.
33	Lack of association between polymorphisms of MASP2 and susceptibility to SARS coronavirus infection.BMC Infect Dis. 2009 May 1;9:51. doi: 10.1186/1471-2334-9-51.
34	Fluorescent Inhibitors as Tools To Characterize Enzymes: Case Study of the Lipid Kinase Phosphatidylinositol 4-Kinase III (PI4KB).J Med Chem. 2017 Jan 12;60(1):119-127. doi: 10.1021/acs.jmedchem.6b01466. Epub 2016 Dec 22.
35	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.
36	TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein.J Virol. 2014 Jan;88(2):1293-307. doi: 10.1128/JVI.02202-13. Epub 2013 Nov 13.
37	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.
38	Severe acute respiratory syndrome coronavirus spike protein counteracts BST2-mediated restriction of virus-like particle release.J Med Virol. 2019 Oct;91(10):1743-1750. doi: 10.1002/jmv.25518. Epub 2019 Jul 10.
39	CD209 (DC-SIGN) -336A>G promoter polymorphism and severe acute respiratory syndrome in Hong Kong Chinese.Hum Immunol. 2010 Jul;71(7):702-7. doi: 10.1016/j.humimm.2010.03.006. Epub 2010 May 4.
40	Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment.J Gen Virol. 2013 Dec;94(Pt 12):2679-2690. doi: 10.1099/vir.0.055533-0. Epub 2013 Sep 28.
41	Functional polymorphisms of the CCL2 and MBL genes cumulatively increase susceptibility to severe acute respiratory syndrome coronavirus infection.J Infect. 2015 Jul;71(1):101-9. doi: 10.1016/j.jinf.2015.03.006. Epub 2015 Mar 27.
42	Design and biological activities of novel inhibitory peptides for SARS-CoV spike protein and angiotensin-converting enzyme 2 interaction.Antiviral Res. 2006 Feb;69(2):70-6. doi: 10.1016/j.antiviral.2005.10.005. Epub 2005 Nov 28.
43	Variation analysis of the severe acute respiratory syndrome coronavirus putative non-structural protein 2 gene and construction of three-dimensional model.Chin Med J (Engl). 2005 May 5;118(9):707-13.
44	Evaluation of a non-prime site substituent and warheads combined with a decahydroisoquinolin scaffold as a SARS 3CL protease inhibitor.Bioorg Med Chem. 2019 Jan 15;27(2):425-435. doi: 10.1016/j.bmc.2018.12.019. Epub 2018 Dec 12.
45	Coronaviridae and SARS-associated coronavirus strain HSR1.Emerg Infect Dis. 2004 Mar;10(3):413-8. doi: 10.3201/eid1003.030683.
46	IL-12 RB1 genetic variants contribute to human susceptibility to severe acute respiratory syndrome infection among Chinese.PLoS One. 2008 May 14;3(5):e2183. doi: 10.1371/journal.pone.0002183.
47	Acquired but reversible loss of erythrocyte complement receptor 1 (CR1, CD35) and its longitudinal alteration in patients with severe acute respiratory syndrome.Clin Exp Immunol. 2005 Jan;139(1):112-9. doi: 10.1111/j.1365-2249.2005.02681.x.
48	Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV).BMC Genomics. 2005 Sep 21;6:132. doi: 10.1186/1471-2164-6-132.
49	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.
50	Polymorphisms in the C-type lectin genes cluster in chromosome 19 and predisposition to severe acute respiratory syndrome coronavirus (SARS-CoV) infection.J Med Genet. 2008 Nov;45(11):752-8. doi: 10.1136/jmg.2008.058966. Epub 2008 Aug 12.
51	Identification and application of self-binding zipper-like sequences in SARS-CoV spike protein.Int J Biochem Cell Biol. 2018 Aug;101:103-112. doi: 10.1016/j.biocel.2018.05.012. Epub 2018 May 22.
52	Chemokine-like factor 1, a novel cytokine, contributes to airway damage, remodeling and pulmonary fibrosis.Chin Med J (Engl). 2004 Aug;117(8):1123-9.
53	Significance of the myxovirus resistance A (MxA) gene -123C>a single-nucleotide polymorphism in suppressed interferon beta induction of severe acute respiratory syndrome coronavirus infection.J Infect Dis. 2010 Jun 15;201(12):1899-908. doi: 10.1086/652799.
54	Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain.Cell Mol Immunol. 2014 Mar;11(2):141-9. doi: 10.1038/cmi.2013.61. Epub 2014 Feb 10.
55	Association of SARS susceptibility with single nucleic acid polymorphisms of OAS1 and MxA genes: a case-control study.BMC Infect Dis. 2006 Jul 6;6:106. doi: 10.1186/1471-2334-6-106.
56	SARS coronavirus protein nsp1 disrupts localization of Nup93 from the nuclear pore complex.Biochem Cell Biol. 2019 Dec;97(6):758-766. doi: 10.1139/bcb-2018-0394. Epub 2019 Apr 3.