Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT85VHW)

• DTT Name: MERS-CoV spike glycoprotein (S)
• Synonyms: MERS-CoV S glycoprotein; MERS-CoV E2; MERS-CoV Peplomer protein
• Gene Name: MERS-CoV S
• BioChemical Class: Betacoronaviruses spike protein family
• UniProt ID: A0A140AYZ5_9BETC
• TTD ID: T88595
• Sequence:
  MIHSVFLLMFLLTPTESYVDVGPDSVKSACIEVDIQQTFFDKTWPRPIDVSKADGIIYPQ
  GRTYSNITITYQGLFPYQGDHGDMYVYSAGHATGTTPQKLFVANYSQDVKQFANGFVVRI
  GAAANSTGTVIISPSTSATIRKIYPAFMLGSSVGNFSDGKMGRFFNHTLVLLPDGCGTLL
  RAFYCILEPRSGNHCPAGNSYTSFATYHTPATDCSDGNYNRNASLNSFKEYFNLRNCTFM
  YTYNITEDEILEWFGITQTAQGVHLFSSRYVDLYGGNMFQFATLPVYDTIKYYSIIPHSI
  RSIQSDRKAWAAFYVYKLQPLTFLLDFSVDGYIRRAIDCGFNDLSQLHCSYESFDVESGV
  YSVSSFEAKPSGSVVEQAEGVECDFSPLLSGTPPQVYNFKRLVFTNCNYNLTKLLSLFSV
  NDFTCSQISPAAIASNCYSSLILDYFSYPLSMKSDLSVSSAGPISQFNYKQSFSNPTCLI
  LATVPHNLTTITKPLKYSYINKCSRLLSDDRTEVPQLVNANQYSPCVSTVPSTVWEDGDY
  YRKQLSPLEGGGWLVASGSTVAMTEQLQMGFGITVQYGTDTNSVCPKLEFANDTKIASQL
  GNCVEYSLYGVSGRGVFQNCTAVGVRQQRFVYDAYQNLVGYYSDDGNYYCLRACVSVPVS
  VIYDKETKTHATLFGSVACEHISSTMSQYSRSTRSMLKRRDSTYGPLQTPVGCVLGLVNS
  SLFVEDCKLPLGQSLCALPDTPSTLTPRSVRSVPGEMRLASIAFNHPIQVDQLNSSYFKL
  SIPTNFSFGVTQEYIQTTIQKVTVDCKQYVCNGFQKCEQLLREYGQFCSKINQALHGANL
  RQDDSVRNLFASVKSSQSSPIIPGFGGDFNLTLLEPVSISTGSRSARSAIEDLLFDKVTI
  ADPGYMQGYDDCMQQGPASARDLICAQYVAGYKVLPPLMDVNMEAAYTSSLLGSIAGVGW
  TAGLSSFAAIPFAQSIFYRLNGVGITQQVLSENQKLIANKFNQALGAMQTGFTTTNEAFR
  KVQDAVNNNAQALSKLASELSNTFGAISASIGDIIQRLDVLEQDAQIDRLINGRLTTLNA
  FVAQQLVRSESAALSAQLAKDKVNECVKAQSKRSGFCGQGTHIVSFVVNAPNGLYFMHVG
  YYPSNHIEVVSAYGLCDAANPTNCIAPVNGYFIKTNNTRIVDEWSYTGSSFYAPEPITSL
  NTKYVAPQVTYQNISTNLPPPLLGNSTGIDFQDELDEFFKNVSTSIPNFGSLTQINTTLL
  DLTYEMLSLQQVVKALNESYIDLKELGNYTYYNKWPWYIWLGFIAGLVALALCVFFILCC
  TGCGTNCMGKLKCNRCCDRYEEYDLEPHKVHVH
• Function: Mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nafamostat	DMU1XOD	Pancreatitis	DC31-DC34	Approved	[1]

2 Discontinued Drugs Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
REGN 3048	DMW08TD	Middle East Respiratory Syndrome (MERS)	1D64	Discontinue in Phase 1 Trial	[2]
REGN 3051	DMLH28J	Middle East Respiratory Syndrome (MERS)	1D64	Discontinue in Phase 1 Trial	[2]

7 Preclinical Drugs Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alpha-Helical lipopeptides FFS	DMATQB7	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[3]
Alpha-Helical lipopeptides IIK	DMVSKQF	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[3]
Alpha-Helical lipopeptides IIS	DM1MGBX	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[3]
Alpha-Helical lipopeptides LLS	DM3WVM4	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[3]
MERS-five-helix bundle	DMG5YRP	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[4]
Peptide P21S10	DMMWQTI	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[5]
PMID26911565-peptide-P9	DMUH012	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[6]

References

• [1] 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.
• [2] Pre- And Postexposure Efficacy of Fully Human Antibodies Against Spike Protein in a Novel Humanized Mouse Model of MERS-CoV Infection. Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8738-43. doi: 10.1073/pnas.1510830112.
• [3] 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.
• [4] Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus. Viruses. 2017 Sep 14;9(9). pii: E255.
• [5] 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.
• [6] A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses. Sci Rep. 2016 Feb 25;6:22008.