Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT1D53B)

• DTT Name: COVID-19 3C-like protease (3CLpro)
• Synonyms: COVID-19 3CL-PRO; COVID-19 3CLp; COVID-19 nsp5
• Gene Name: COVID-19 rep
• BioChemical Class: Coronaviruses polyprotein 1ab family
• UniProt ID: R1AB_SARS2 (3264-3569)
• TTD ID: T88015
• EC Number: EC 3.4.22.69
• Sequence:
  SGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDVVYCPRHVICTSEDMLNPNYEDLLIR
  KSNHNFLVQAGNVQLRVIGHSMQNCVLKLKVDTANPKTPKYKFVRIQPGQTFSVLACYNG
  SPSGVYQCAMRPNFTIKGSFLNGSCGSVGFNIDYDCVSFCYMHHMELPTGVHAGTDLEGN
  FYGPFVDRQTAQAAGTDTTITVNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYE
  PLTQDHVDILGPLSAQTGIAVLDMCASLKELLQNGMNGRTILGSALLEDEFTPFDVVRQC
  SGVTFQ
• 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
BOCEPREVIR	DMBSHMF	Hepatitis C virus infection	1E51.1	Approved	[2]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-07817883	DMNX86H	Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 1	[3]

1 Preclinical Drugs Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GC376	DMR1CLY	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[2]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GRL001	DM19T2V	Coronavirus infection	1D92	Preclinical	[4]

References

• [1] Coronavirus puts drug repurposing on the fast track. Nat Biotechnol. 2020 Apr;38(4):379-381.
• [2] Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. 2020. April 20. doi: https://doi.org/10.1101/2020.04.20.051581
• [3] ClinicalTrials.gov (NCT05580003) COVID-19: A MULTIPART, PHASE 1 STUDY WITH RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE-DOSE ESCALATION TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-07817883 AND OPTIONAL OPEN-LABEL, RANDOMIZED STUDY TO EVALUATE RELATIVE BIOAVAILABILITY AND FOOD EFFECT OF SOLID ORAL FORMULATION AND OPTIONAL OPEN-LABEL, NON-RANDOMIZED STUDY TO EVALUATE METABOLISM AND EXCRETION OF PF-07817883 AND OPTIONAL RANDOMIZED, OPEN-LABEL STUDY TO ASSESS THE EFFECT OF PF-07817883 ON PHARMACOKINETICS OF MIDAZOLAM IN HEALTHY ADULT PARTICIPANTS. U.S.National Institutes of Health.
• [4] Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.