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CoV 3C-like (main) protease

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Target not currently curated in GtoImmuPdb

Target id: 3111

Nomenclature: CoV 3C-like (main) protease

Family: Coronavirus (CoV) proteins

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
SARS-CoV-2 - 306
SARS-CoV - 306
Gene and Protein Information Comments
The SARS-CoV main protease (Mpro) is a 306 amino acid cysteine protease that is encoded in the viral RNA replicase gene. It is amino acids 3241-3546 of the full length SARS-CoV polyprotein (3919 amino acids).
The SARS-CoV-2 Mpro is also 306 amino acids. The provisional RefSeq YP_009725301 has been allocated to SARS-CoV-2 M6LU7 [16]. The amino acid sequence for Mpro from the PDB entry has been submitted to the NCBI as 6LU7_A (Chain A, SARS-CoV-2 main protease). A UniProt ID will be released with UniProt release 2020_02 (due April 22nd, 2020). Pre-release information provides the ID P0DTD1 for the complete SARS-CoV-2 replicase polyprotein (length 7096 amino acids). SARS-CoV-2 Mpro is amino acids 3264-3569 of the full length polyprotein.
Previous and Unofficial Names Click here for help
3c-like proteinase | SARS-CoV-2 Mpro | Chain A, 3c-like Proteinase | 3CL protease | Mpro | nsp5
Database Links Click here for help
ChEMBL Target CHEMBL3927 (SARS-CoV)
RefSeq Protein
UniProtKB P0C6U8 (SARS-CoV)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure (monoclinic form) of the complex resulting from the reaction between SARS-CoV-2 (2019-nCoV) main protease and tert-butyl (1-((S)-1-(((S)-4-(benzylamino)-3,4-dioxo-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-2-oxo-1,2-dihydropyridin-3-yl)carbamate (alpha-ketoamide 13b)
PDB Id:  6Y2F
Ligand:  compound 13b [PMID: 32198291]
Resolution:  1.95Å
Species:  SARS-CoV-2
References:  41
Image of receptor 3D structure from RCSB PDB
Description:  The crystal structure of COVID-19 main protease in complex with an inhibitor N3 (PRD_002214).
PDB Id:  6LU7
Ligand:  PRD_002214
Resolution:  2.16Å
Species:  SARS-CoV-2
References:  16
Image of receptor 3D structure from RCSB PDB
Description:  The crystal structure of COVID-19 main protease in complex with an inhibitor 11a
PDB Id:  6LZE
Ligand:  compound 11a [PMID: 32321856]
Resolution:  1.5Å
Species:  SARS-CoV-2
References:  9
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of SARS-CoV 3C-like protease in apo form
PDB Id:  3VB3
Resolution:  2.2Å
Species:  SARS-CoV
References:  7
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of SARS coronavirus 3CL protease inhibitor complex
PDB Id:  2GX4
Ligand:  TG-0205221
Resolution:  1.93Å
Species:  SARS-CoV
References:  36
Image of receptor 3D structure from RCSB PDB
Description:  Covalent complex of SARS-CoV main protease with N-[(2S)-1-({(2S,3S)-3,4-dihydroxy-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}amino)-4-methyl-1-oxopentan-2-yl]-4-methoxy-1H-indole-2-carboxamide
PDB Id:  6XHL
Ligand:  PF-00835231
Resolution:  1.47Å
Species:  SARS-CoV
References:  15
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of SARS-CoV-2 main protease in complex with MI-23
PDB Id:  7D3I
Ligand:  MI-23
Resolution:  2.0Å
Species:  SARS-CoV-2
References:  24
Image of receptor 3D structure from RCSB PDB
Description:  Structure of SARS-CoV2 3CL protease covalently bound to peptidomimetic inhibitor
PDB Id:  7MBI
Ligand:  compound 15l [PMID: 34242027]
Resolution:  2.15Å
Species:  SARS-CoV-2
References: 
Image of receptor 3D structure from RCSB PDB
Description:  The crystal structure of SARS-CoV-2 Main Protease in complex with masitinib
PDB Id:  7JU7
Ligand:  masitinib
Resolution:  1.6Å
Species:  SARS-CoV-2
References:  11
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the SARS-CoV-2 (COVID-19) main protease in complex with inhibitor UAWJ9-36-3
PDB Id:  7lyi
Ligand:  UAWJ9-36-3
Resolution:  1.9Å
Species:  SARS-CoV-2
References:  33
EC number (SARS-CoV-2)
3.4.22.69

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PF-07321332 Small molecule or natural product SARS-CoV-2 Inhibition 9.6 pKi 21
⤷ pKi 9.6 (Ki 2.71x10-10 M) [21]
Description: Determined in vitro, in a TR-FRET enzyme assay
PF-00835231 Small molecule or natural product Ligand has a PDB structure SARS-CoV Inhibition 8.4 pKi 15
⤷ pKi 8.4 (Ki 4x10-9 M) [15]
Description: Determined using an in vitro SARS-CoV-1 3CLpro FRET assay.
YH-53 Small molecule or natural product Ligand has a PDB structure SARS-CoV Inhibition 8.2 pKi 27
⤷ pKi 8.2 (Ki 6.3x10-9 M) [27]
compound 17 [PMID: 33655614] Small molecule or natural product SARS-CoV-2 Inhibition 8.0 pKi 5
⤷ pKi 8.0 (Ki 1x10-8 M) [5]
compound 8 [PMID: 33655614] Small molecule or natural product SARS-CoV-2 Inhibition 7.6 pKi 5
⤷ pKi 7.6 (Ki 2.4x10-8 M) [5]
YH-53 Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 7.5 – 7.8 pKi 14,17
⤷ pKi 7.8 (Ki 1.76x10-8 M) [14]
pKi 7.5 (Ki 3.47x10-8 M) [17]
CDD-1976 Small molecule or natural product SARS-CoV-2 Inhibition 7.4 pKi 6
⤷ pKi 7.4 (Ki 3.7x10-8 M) [6]
TG-0205221 Peptide Ligand has a PDB structure SARS-CoV Inhibition 7.3 pKi 36
⤷ pKi 7.3 (Ki 5.3x10-8 M) [36]
TG-0203770 Small molecule or natural product Ligand has a PDB structure SARS-CoV Inhibition 7.2 pKi 19
⤷ pKi 7.2 (Ki 5.8x10-8 M) [19]
compound 3 [PMID: 16884309] Peptide SARS-CoV Inhibition 6.2 pKi 36
⤷ pKi 6.2 (Ki 6.6x10-7 M) [36]
boceprevir Small molecule or natural product Approved drug SARS-CoV-2 Inhibition 5.9 pKi 20
⤷ pKi 5.9 (Ki 1.18x10-6 M) [20]
Description: Inhibition of recombinat enzyme in vitro.
compound 17 [PMID: 33655614] Small molecule or natural product SARS-CoV Inhibition 8.1 pIC50 4
⤷ pIC50 8.1 (IC50 7x10-9 M) [4]
MI-23 Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 8.1 pIC50 24
⤷ pIC50 8.1 (IC50 7.6x10-9 M) [24]
Description: Inhibition of recombinant enzyme in vitro
PF-00835231 Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 8.1 pIC50 30
⤷ pIC50 8.1 (IC50 8x10-9 M) [30]
TG-0205221 Peptide Ligand has a PDB structure SARS-CoV-2 Inhibition 8.1 pIC50 30
⤷ pIC50 8.1 (IC50 9x10-9 M) [30]
MI-09 Small molecule or natural product SARS-CoV-2 Inhibition 7.8 pIC50 24
⤷ pIC50 7.8 (IC50 1.52x10-8 M) [24]
Description: Inhibition of recombinant enzyme in vitro
MI-30 Small molecule or natural product SARS-CoV-2 Inhibition 7.8 pIC50 24
⤷ pIC50 7.8 (IC50 1.72x10-8 M) [24]
Description: Inhibition of recombinant enzyme in vitro
PF-07321332 Small molecule or natural product SARS-CoV-2 Inhibition 7.7 pIC50
⤷ pIC50 7.7 (IC50 1.9x10-8 M) Value provided at a session by Dafydd Owen (Pfizer) at the ACS Spring 2021 meeting; not yet published
compound 15l [PMID: 34242027] Small molecule or natural product SARS-CoV-2 Inhibition 7.7 pIC50 2
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [2]
Description: Inhibition of enzymatic activity in a FRET-based kinetic assay.
CCF981 Small molecule or natural product SARS-CoV Inhibition 7.7 pIC50 13
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [13]
compound 11a [PMID: 32321856] Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 7.3 – 7.8 pIC50 9,30
⤷ pIC50 7.8 (IC50 1.4x10-8 M) [30]
pIC50 7.3 (IC50 5.3x10-8 M) [9]
Description: In vitro inhibition of recombinant SARS-CoV-2 Mpro enzymatic activity.
compound 11b [PMID: 32321856] Small molecule or natural product SARS-CoV-2 Inhibition 7.4 – 7.6 pIC50 9,30
⤷ pIC50 7.6 (IC50 2.3x10-8 M) [30]
pIC50 7.4 (IC50 4x10-8 M) [9]
Description: In vitro inhibition of recombinant SARS-CoV-2 Mpro enzymatic activity.
GRL-0496 Small molecule or natural product SARS-CoV Inhibition 7.5 pIC50 12
⤷ pIC50 7.5 (IC50 3x10-8 M) [12]
MP13 Small molecule or natural product SARS-CoV-2 Inhibition 7.5 pIC50 35
⤷ pIC50 7.5 (IC50 3.3x10-8 M) [35]
example 4 [WO2017114509] Small molecule or natural product SARS-CoV-2 Inhibition 7.5 pIC50 8
⤷ pIC50 7.5 (IC50 3.4x10-8 M) [8]
ML1000 Small molecule or natural product SARS-CoV-2 Inhibition 7.5 pIC50 32
⤷ pIC50 7.5 (IC50 3.4x10-8 M) [32]
compound 19 [Zhang et al., 2021] Small molecule or natural product SARS-CoV-2 Inhibition 7.4 pIC50 37
⤷ pIC50 7.4 (IC50 4.4x10-8 M) [37]
Description: Inhibition of Mpro proteolytic activity, determined using a substrate peptide cleavage FRET assay.
GC-376 Small molecule or natural product SARS-CoV Inhibition 7.3 pIC50 31
⤷ pIC50 7.3 (IC50 5x10-8 M) [31]
GRL-0496 Small molecule or natural product SARS-CoV-2 Inhibition 7.3 pIC50 23
⤷ pIC50 7.3 (IC50 5x10-8 M) [23]
UAWJ9-36-3 Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 7.3 pIC50 33
⤷ pIC50 7.3 (IC50 5.4x10-8 M) [33]
compound 21 [Zhang et al., 2021] Small molecule or natural product SARS-CoV-2 Inhibition 7.2 pIC50 37
⤷ pIC50 7.2 (IC50 6.1x10-8 M) [37]
Description: Inhibition of Mpro proteolytic activity, determined using a substrate peptide cleavage FRET assay.
compound 17 [PMID: 33655614] Small molecule or natural product SARS-CoV-2 Inhibition 7.2 pIC50 30
⤷ pIC50 7.2 (IC50 6.5x10-8 M) [30]
CCF981 Small molecule or natural product SARS-CoV-2 Inhibition 7.2 pIC50 13
⤷ pIC50 7.2 (IC50 6.8x10-8 M) [13]
GC-373 Peptide SARS-CoV Inhibition 7.2 pIC50 31
⤷ pIC50 7.2 (IC50 7x10-8 M) [31]
GC-376 Small molecule or natural product SARS-CoV-2 Inhibition 6.7 – 7.5 pIC50 20,31,33
⤷ pIC50 7.5 (IC50 3x10-8 M) [20]
pIC50 7.4 (IC50 4.1x10-8 M) [33]
pIC50 6.7 (IC50 1.9x10-7 M) [31]
compound 2i [PMID: 23245752] Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 7.0 pIC50 30
⤷ pIC50 7.0 (IC50 9.4x10-8 M) [30]
UAWJ9-36-3 Small molecule or natural product Ligand has a PDB structure SARS-CoV Inhibition 7.0 pIC50 33
⤷ pIC50 7.0 (IC50 9.9x10-8 M) [33]
GC-373 Peptide SARS-CoV-2 Inhibition 6.4 – 7.4 pIC50 30-31
⤷ pIC50 7.4 (IC50 4.2x10-8 M) [30]
pIC50 6.4 (IC50 4x10-7 M) [31]
compound 5 [Zhang et al., 2021] Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 6.8 pIC50 38
⤷ pIC50 6.8 (IC50 1.4x10-7 M) [38]
compound 6e [PMID: 32747425] Small molecule or natural product SARS-CoV-2 Inhibition 6.8 pIC50 25
⤷ pIC50 6.8 (IC50 1.7x10-7 M) [25]
compound 11r [PMID: 32045235] Small molecule or natural product SARS-CoV-2 Inhibition 6.7 pIC50 40
⤷ pIC50 6.7 (IC50 1.8x10-7 M) [40]
compound 2a [PMID: 34213885] Small molecule or natural product SARS-CoV-2 Inhibition 6.7 pIC50 10
⤷ pIC50 6.7 (IC50 1.8x10-7 M) [10]
Description: Determined in a FRET enzyme assay.
walrycin B Small molecule or natural product SARS-CoV-2 Inhibition 6.6 pIC50 42
⤷ pIC50 6.6 (IC50 2.6x10-7 M) [42]
Description: Inhibition determined in an HTS fluorogenic enzyme activity assay.
compound 3 [PMID: 16884309] Peptide SARS-CoV-2 Inhibition 6.5 pIC50 30
⤷ pIC50 6.5 (IC50 2.86x10-7 M) [30]
DAV-CRI-14a23e73-1 Small molecule or natural product SARS-CoV-2 Inhibition 6.3 pIC50 23
⤷ pIC50 6.3 (IC50 4.7x10-7 M) [23]
compound 6j [PMID: 32747425] Small molecule or natural product SARS-CoV-2 Inhibition 6.3 pIC50 25
⤷ pIC50 6.3 (IC50 4.8x10-7 M) [25]
compound 13b [PMID: 32198291] Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 6.2 pIC50 40
⤷ pIC50 6.2 (IC50 6.7x10-7 M) [40]
compound 6e [PMID: 32747425] Small molecule or natural product SARS-CoV Inhibition 6.1 pIC50 25
⤷ pIC50 6.1 (IC50 9x10-7 M) [25]
compound 6j [PMID: 32747425] Small molecule or natural product SARS-CoV Inhibition 5.9 pIC50 25
⤷ pIC50 5.9 (IC50 1.2x10-6 M) [25]
boceprevir Small molecule or natural product Approved drug SARS-CoV Inhibition 5.6 – 6.0 pIC50 1,3
⤷ pIC50 5.6 – 6.0 (IC50 2.5x10-6 – 9.49x10-7 M) [1,3]
compound 2i [PMID: 23245752] Small molecule or natural product Ligand has a PDB structure SARS-CoV Inhibition 5.8 pIC50 18
⤷ pIC50 5.8 (IC50 1.7x10-6 M) [18]
MG-132 Peptide Ligand has a PDB structure SARS-CoV-2 Inhibition 5.4 pIC50 20
⤷ pIC50 5.4 (IC50 3.9x10-6 M) [20]
boceprevir Small molecule or natural product Approved drug SARS-CoV-2 Inhibition 5.4 pIC50 20
⤷ pIC50 5.4 (IC50 4.13x10-6 M) [20]
ML300 Small molecule or natural product Ligand has a PDB structure SARS-CoV Inhibition 5.3 – 5.4 pIC50 13,29
⤷ pIC50 5.4 (IC50 4.1x10-6 M) [29]
pIC50 5.3 (IC50 4.45x10-6 M) [13]
ML300 Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 5.3 pIC50 13
⤷ pIC50 5.3 (IC50 4.99x10-6 M) [13]
MG-115 Peptide SARS-CoV-2 Inhibition 5.2 pIC50 20
⤷ pIC50 5.2 (IC50 6.14x10-6 M) [20]
PRD_002214 Small molecule or natural product SARS-CoV Inhibition 5.1 pIC50 34
⤷ pIC50 5.1 (IC50 9x10-6 M) [34]
calpeptin Peptide SARS-CoV-2 Inhibition 5.0 pIC50 20
⤷ pIC50 5.0 (IC50 1.069x10-5 M) [20]
telaprevir Small molecule or natural product SARS-CoV-2 Inhibition 4.9 pIC50 22
⤷ pIC50 4.9 (IC50 1.147x10-5 M) [22]
Z-FA-FMK Peptide Immunopharmacology Ligand SARS-CoV-2 Inhibition 4.9 pIC50 42
⤷ pIC50 4.9 (IC50 1.139x10-5 M) [42]
Description: Inhibition determined in an HTS fluorogenic enzyme activity assay.
compound 25c [PMID: 23747811] Peptide SARS-CoV Inhibition 4.7 pIC50 28
⤷ pIC50 4.7 (IC50 2.1x10-5 M) [28]
PRD_002214 Small molecule or natural product SARS-CoV-2 Irreversible inhibition - - 16
⤷ [16]
View species-specific inhibitor tables
Inhibitor Comments
PRD_002214 (N3) inhibits SARS-CoV-2 plaque formation in Vero cell culture with an IC50 of 16.77 μM [16].
The MERS-CoV inhibitor compound 11r [PMID: 32045235] is active against SARS-CoV-2 [39].
Baker et al. (2021) performed a large scale repurposing screen, which corroborated the inhibitory activity of boceprevir (and other hepatitis C NS3/4A protease inhibitors) against SARS-CoV-2 Mpro [3].
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
GC-376 Small molecule or natural product SARS-CoV - 7.4 pIC50 33
⤷ pIC50 7.4 (IC50 4.1x10-8 M) [33]
General Comments
The coronavirus (CoV) main proteases (Mpro) are cysteine proteases that are encoded in the viral RNA replicase gene. Mpro catalyses the proteolytic processing (cleavage) of replicase precursor polyproteins in to discrete functional proteins. In total There are 11 Mpro cleavage site within the C-terminus of the replicase polyprotein. Mpro plays a central role in the viral life cycle, and in light of evidence from other coronaviruses, SARS-CoV Mpro was a lead target for antiviral drug discovery. Many of the compounds that were discovered to inhibit the activity of MERS- and SARS-CoV Mpro enzymes have been tested for activity against SARS-CoV-2 [26].

Although Mpro is strictly a component of the CoV replicase polyprotein(s) 1a and 1ab, we have included it as a separate entity to allow us to more sensibly curate pharmacological information (particularly regarding inhibitor development) that is specific for this protease, and to facilitate data retrieval.

References

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1. Anson BJ, Chapman ME, Lendy EK, Pshenychnyi S, D’Aquila RT, Satchell KJF, Mesecar AD. (2020) Broad-spectrum inhibition of coronavirus main and papain-like proteases by HCV drugs. Nature Research, PrePrint, Under Review. DOI: 10.21203/rs.3.rs-26344/v1

2. Bai B, Belovodskiy A, Hena M, Kandadai AS, Joyce MA, Saffran HA, Shields JA, Khan MB, Arutyunova E, Lu J et al.. (2021) Peptidomimetic α-Acyloxymethylketone Warheads with Six-Membered Lactam P1 Glutamine Mimic: SARS-CoV-2 3CL Protease Inhibition, Coronavirus Antiviral Activity, and in Vitro Biological Stability. J Med Chem, [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.1c00616 [PMID:34242027]

3. Baker JD, Uhrich RL, Kraemer GC, Love JE, Kraemer BC. (2021) A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease. PLoS One, 16 (2): e0245962. [PMID:33524017]

4. Botyanszki J, Catalano G, Chong PY, Dickson H, Jin Q, Leivers A, Maynard A, Liao X, Miller J, Shotwell JB et al.. (2018) Compounds that inhibit 3c and 3cl proteases and methods of use thereof. Patent number: WO2018042343A2. Assignee: Glaxosmithkline Intellectual Property (No.2) Limited. Priority date: 30/08/2016. Publication date: 08/03/2018.

5. Breidenbach J, Lemke C, Pillaiyar T, Schäkel L, Al Hamwi G, Diett M, Gedschold R, Geiger N, Lopez V, Mirza S et al.. (2021) Targeting the Main Protease of SARS-CoV-2: From the Establishment of High Throughput Screening to the Design of Tailored Inhibitors. Angew Chem Int Ed Engl, [Epub ahead of print]. DOI: 0.1002/anie.202016961 [PMID:33655614]

6. Chamakuri S, Lu S, Ucisik MN, Bohren KM, Chen YC, Du HC, Faver JC, Jimmidi R, Li F, Li JY et al.. (2021) DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 Mpro inhibitors. Proc Natl Acad Sci U S A, 118 (36). DOI: 10.1073/pnas.2111172118 [PMID:34426525]

7. Chuck CP, Chen C, Ke Z, Wan DC, Chow HF, Wong KB. (2013) Design, synthesis and crystallographic analysis of nitrile-based broad-spectrum peptidomimetic inhibitors for coronavirus 3C-like proteases. Eur J Med Chem, 59: 1-6. [PMID:23202846]

8. Dai W, Jochmans D, Xie H, Yang H, Li J, Su H, Chang D, Wang J, Peng J, Zhu L et al.. (2021) Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV-2. J Med Chem, [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.0c02258 [PMID:33872498]

9. Dai W, Zhang B, Jiang XM, Su H, Li J, Zhao Y, Xie X, Jin Z, Peng J, Liu F et al.. (2020) Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science, 368 (6497): 1331-1335. [PMID:32321856]

10. Dampalla CS, Kim Y, Bickmeier N, Rathnayake AD, Nguyen HN, Zheng J, Kashipathy MM, Baird MA, Battaile KP, Lovell S et al.. (2021) Structure-Guided Design of Conformationally Constrained Cyclohexane Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 3CL Protease. J Med Chem, [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.1c00319 [PMID:34213885]

11. Drayman R, DeMarco JK, Jones KA, Azizi S-A, Froggatt HM, Tan K, Maltseva NI, Chen S, Nicolaescu V, Dvorkin S et al.. (2021) Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2. Science, {Epub ahead of print]. DOI: 10.1126/science.abg5827

12. Ghosh AK, Gong G, Grum-Tokars V, Mulhearn DC, Baker SC, Coughlin M, Prabhakar BS, Sleeman K, Johnson ME, Mesecar AD. (2008) Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors. Bioorg Med Chem Lett, 18 (20): 5684-8. [PMID:18796354]

13. Han SH, Goins CM, Arya T, Shin WJ, Maw J, Hooper A, Sonawane DP, Porter MR, Bannister BE, Crouch RD et al.. (2021) Structure-Based Optimization of ML300-Derived, Noncovalent Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus 3CL Protease (SARS-CoV-2 3CLpro). J Med Chem, [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.1c00598 [PMID:34347470]

14. Hattori SI, Higashi-Kuwata N, Hayashi H, Allu SR, Raghavaiah J, Bulut H, Das D, Anson BJ, Lendy EK, Takamatsu Y et al.. (2021) A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication. Nat Commun, 12 (1): 668. [PMID:33510133]

15. Hoffman RL, Kania RS, Brothers MA, Davies JF, Ferre RA, Gajiwala KS, He M, Hogan RJ, Kozminski K, Li LY et al.. (2020) Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19. J Med Chem, 63 (21): 12725-12747. [PMID:33054210]

16. Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhang B, Li X, Zhang L, Peng C, Duan Y. (2020) Structure of Mpro from COVID-19 virus and discovery of its inhibitors. bioRxiv, Preprint. DOI: 10.1101/2020.02.26.964882

17. Konno S, Kobayashi K, Senda M, Funai Y, Seki Y, Tamai A, Schakel L, Sakata K, Pillaiyar T, Taguchi A et al.. (2021) 3CL Protease Inhibitors with an Electrophilic Arylketone Moiety as Anti-SARS-CoV-2 Agents. Journal of Medicinal Chemistry, [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.1c00665 [PMID:34313428]

18. Konno S, Thanigaimalai P, Yamamoto T, Nakada K, Kakiuchi R, Takayama K, Yamazaki Y, Yakushiji F, Akaji K, Kiso Y et al.. (2013) Design and synthesis of new tripeptide-type SARS-CoV 3CL protease inhibitors containing an electrophilic arylketone moiety. Bioorg Med Chem, 21 (2): 412-24. [PMID:23245752]

19. Lee CC, Kuo CJ, Ko TP, Hsu MF, Tsui YC, Chang SC, Yang S, Chen SJ, Chen HC, Hsu MC et al.. (2009) Structural basis of inhibition specificities of 3C and 3C-like proteases by zinc-coordinating and peptidomimetic compounds. J Biol Chem, 284 (12): 7646-55. [PMID:19144641]

20. Ma C, Sacco MD, Hurst B, Townsend JA, Hu Y, Szeto T, Zhang X, Tarbet B, Marty MT, Chen Y et al.. (2020) Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. Cell Res, 30 (8): 678-692. DOI: 10.1038/s41422-020-0356-z [PMID:32541865]

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