Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTWOH4Q)

• DTT Name: MERS-CoV 3C-like proteinase (3CLpro)
• Synonyms: MERS-CoV 3C-like proteinase; MERS-CoV 3CLp; MERS-CoV 3CL-PRO; MERS-CoV 3CLpro
• Gene Name: MERS-CoV rep
• BioChemical Class: Coronaviruses polyprotein 1ab family
• UniProt ID: R1AB_CVEMC (3248-3553)
• TTD ID: T89592
• EC Number: EC 3.4.22.-
• Sequence:
  SGLVKMSHPSGDVEACMVQVTCGSMTLNGLWLDNTVWCPRHVMCPADQLSDPNYDALLIS
  MTNHSFSVQKHIGAPANLRVVGHAMQGTLLKLTVDVANPSTPAYTFTTVKPGAAFSVLAC
  YNGRPTGTFTVVMRPNYTIKGSFLCGSCGSVGYTKEGSVINFCYMHQMELANGTHTGSAF
  DGTMYGAFMDKQVHQVQLTDKYCSVNVVAWLYAAILNGCAWFVKPNRTSVVSFNEWALAN
  QFTEFVGTQSVDMLAVKTGVAIEQLLYAIQQLYTGFQGKQILGSTMLEDEFTPEDVNMQI
  MGVVMQ
• Function: Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP).

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lopinavir	DMITQS0	Human immunodeficiency virus infection	1C62	Approved	[2]

6 Preclinical Drugs Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GC376	DMR1CLY	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[3]
GC813	DM7PBJC	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[1]
GRL-001	DMVB1PD	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[2]
PMID26868298-compound-N3	DMQFUCD	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[2]
PMID27240464-compound-3f	DMPC29W	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[4]
PMID28216367-compound-6d	DMPWUFT	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[5]

References

• [1] Structure-guided Design of Potent and Permeable Inhibitors of MERS Coronavirus 3CL Protease That Utilize a Piperidine Moiety as a Novel Design Element Eur J Med Chem. 2018 Apr 25;150:334-346.
• [2] Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
• [3] 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.
• [4] Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors. Bioorg Med Chem. 2016 Jul 1;24(13):3035-3042.
• [5] Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CLPro inhibitors. Antiviral Res. 2017 May;141:101-106.