Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZ3COY)

• DTT Name: COVID-19 spike glycoprotein (S)
• Synonyms: COVID-19 S glycoprotein; COVID-19 E2; COVID-19 Peplomer protein
• Gene Name: COVID-19 S
• BioChemical Class: Betacoronaviruses spike protein family
• UniProt ID: SPIKE_SARS2
• TTD ID: T87374
• 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.
• Reactome Pathway:
  Maturation of spike protein (R-HSA-9694548)
  Attachment and Entry (R-HSA-9694614)
  Translation of Structural Proteins (R-HSA-9694635)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  Virion Assembly and Release (R-HSA-9694322)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK4182136	DMYH2FI	Coronavirus Disease 2019 (COVID-19)	1D6Y	Approved in EU	[2]
Nafamostat	DMU1XOD	Pancreatitis	DC31-DC34	Approved	[1]
Toremifene	DMQYUWG	Breast cancer	2C60-2C65	Approved	[3]

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY-CoV555	DM6LVCQ	Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[4]
REGN-COV2	DM0KBML	Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[5]
JS016	DMGEZVF	Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 1/2	[6]
GSK4182137	DMJJW2Y	Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 1	[2]
REGN3048	DM0E3ZG	Coronavirus infection	1D92	Phase 1	[7]
REGN3051	DM7LIV2	Coronavirus infection	1D92	Phase 1	[7]

3 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
m337	DM7HUVB	Coronavirus infection	1D92	Preclinical	[8]
MERS-27	DMVGIB4	Coronavirus infection	1D92	Preclinical	[8]
MERS-4	DMS6KT8	Coronavirus infection	1D92	Preclinical	[8]

References

• [1] Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020 Mar;19(3):149-150.
• [2] Clinical pipeline report, company report or official report of GlaxoSmithKline
• [3] Repurposing of FDA-Approved Toremifene to Treat COVID-19 by Blocking the Spike Glycoprotein and NSP14 of SARS-CoV-2. June 5, 2020.
• [4] Neutralizing Antibody LY-CoV555 for Outpatient Covid-19. Reply. N Engl J Med. 2021 Jan 14;384(2):189.
• [5] REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):238-251.
• [6] Clinical pipeline report, company report or official report of Lilly.
• [7] Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets. Antiviral Res. 2018 Aug;156:64-71.
• [8] Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.