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CoV 3C-like (main) protease

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Target id: 3111

Nomenclature: CoV 3C-like (main) protease

Family: Coronavirus (CoV) proteins

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 [23]. 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
RefSeq Protein
UniProtKB
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of SARS-CoV-2 3CL protease in complex with inhibitor 10c
PDB Id:  7T49
Ligand:  compound 10c [Dampalla et al., 2022]
Resolution:  1.75Å
Species:  SARS-CoV-2
References:  14
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:  53
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:  23
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:  12
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:  10
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:  48
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:  22
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:  33
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:  17
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:  45
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332
PDB Id:  7VH8
Ligand:  nirmatrelvir
Resolution:  1.59Å
Species:  SARS-CoV-2
References:  54
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:  3
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
compound 19 [PMID: 35142215] Small molecule or natural product SARS-CoV-2 Inhibition 7.4 pKd 27
pKd 7.4 (Kd 3.8x10-8 M) [27]
Description: Binding affinity
nirmatrelvir Small molecule or natural product Approved drug SARS-CoV-2 Inhibition 9.6 pKi 30
pKi 9.6 (Ki 2.71x10-10 M) [30]
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 22
pKi 8.4 (Ki 4x10-9 M) [22]
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 36
pKi 8.2 (Ki 6.3x10-9 M) [36]
compound 17 [PMID: 33655614] Small molecule or natural product SARS-CoV-2 Inhibition 8.0 pKi 6
pKi 8.0 (Ki 1x10-8 M) [6]
compound 8 [PMID: 33655614] Small molecule or natural product SARS-CoV-2 Inhibition 7.6 pKi 6
pKi 7.6 (Ki 2.4x10-8 M) [6]
YH-53 Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 7.5 – 7.8 pKi 19,21,24
pKi 7.8 (Ki 1.76x10-8 M) [19,21]
pKi 7.5 (Ki 3.47x10-8 M) [24]
CDD-1976 Small molecule or natural product SARS-CoV-2 Inhibition 7.4 pKi 7
pKi 7.4 (Ki 3.7x10-8 M) [7]
TG-0205221 Peptide Ligand has a PDB structure SARS-CoV Inhibition 7.3 pKi 48
pKi 7.3 (Ki 5.3x10-8 M) [48]
TG-0203770 Small molecule or natural product Ligand has a PDB structure SARS-CoV Inhibition 7.2 pKi 26
pKi 7.2 (Ki 5.8x10-8 M) [26]
compound 7d [PMID: 34528437] Small molecule or natural product SARS-CoV-2 Inhibition 7.1 pKi 19
pKi 7.1 (Ki 7.3x10-8 M) [19]
compound 3 [PMID: 16884309] Peptide SARS-CoV Inhibition 6.2 pKi 48
pKi 6.2 (Ki 6.6x10-7 M) [48]
boceprevir Small molecule or natural product Approved drug SARS-CoV-2 Inhibition 5.9 pKi 28
pKi 5.9 (Ki 1.18x10-6 M) [28]
Description: Inhibition of recombinat enzyme in vitro.
Z-AVLD-FMK Peptide SARS-CoV-2 Inhibition 9.1 pIC50 29
pIC50 9.1 (IC50 8x10-10 M) [29]
Description: Inhibition in a FRET-based enzyme activity assay
compound 17 [PMID: 33655614] Small molecule or natural product SARS-CoV Inhibition 8.1 pIC50 5
pIC50 8.1 (IC50 7x10-9 M) [5]
MI-23 Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 8.1 pIC50 33
pIC50 8.1 (IC50 7.6x10-9 M) [33]
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 41
pIC50 8.1 (IC50 8x10-9 M) [41]
TG-0205221 Peptide Ligand has a PDB structure SARS-CoV-2 Inhibition 8.1 pIC50 41
pIC50 8.1 (IC50 9x10-9 M) [41]
ensitrelvir Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 7.9 pIC50 40
pIC50 7.9 (IC50 1.3x10-8 M) [40]
MI-09 Small molecule or natural product SARS-CoV-2 Inhibition 7.8 pIC50 33
pIC50 7.8 (IC50 1.52x10-8 M) [33]
Description: Inhibition of recombinant enzyme in vitro
MI-30 Small molecule or natural product SARS-CoV-2 Inhibition 7.8 pIC50 33
pIC50 7.8 (IC50 1.72x10-8 M) [33]
Description: Inhibition of recombinant enzyme in vitro
compound 15l [PMID: 34242027] Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 7.7 pIC50 3
pIC50 7.7 (IC50 1.9x10-8 M) [3]
Description: Inhibition of enzymatic activity in a FRET-based kinetic assay.
CCF981 Small molecule or natural product SARS-CoV Inhibition 7.7 pIC50 20
pIC50 7.7 (IC50 1.9x10-8 M) [20]
example 100 [WO2022043374] Small molecule or natural product SARS-CoV-2 Inhibition 7.6 pIC50 8
pIC50 7.6 (IC50 2.4x10-8 M) [8]
nirmatrelvir Small molecule or natural product Approved drug SARS-CoV-2 Inhibition 7.5 – 7.7 pIC50 27
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
pIC50 7.5 (IC50 3.3x10-8 M) [27]
compound 11a [PMID: 32321856] Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 7.3 – 7.8 pIC50 12,41
pIC50 7.8 (IC50 1.4x10-8 M) [41]
pIC50 7.3 (IC50 5.3x10-8 M) [12]
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 12,41
pIC50 7.6 (IC50 2.3x10-8 M) [41]
pIC50 7.4 (IC50 4x10-8 M) [12]
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 18
pIC50 7.5 (IC50 3x10-8 M) [18]
example 100 [WO2022043374] Small molecule or natural product SARS-CoV Inhibition 7.5 pIC50 8
pIC50 7.5 (IC50 3.1x10-8 M) [8]
MP13 Small molecule or natural product SARS-CoV-2 Inhibition 7.5 pIC50 47
pIC50 7.5 (IC50 3.3x10-8 M) [47]
example 4 [WO2017114509] Small molecule or natural product SARS-CoV-2 Inhibition 7.5 pIC50 11
pIC50 7.5 (IC50 3.4x10-8 M) [11]
ML1000 Small molecule or natural product SARS-CoV-2 Inhibition 7.5 pIC50 44
pIC50 7.5 (IC50 3.4x10-8 M) [44]
compound 19 [Zhang et al., 2021] Small molecule or natural product SARS-CoV-2 Inhibition 7.4 pIC50 49
pIC50 7.4 (IC50 4.4x10-8 M) [49]
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 42
pIC50 7.3 (IC50 5x10-8 M) [42]
GRL-0496 Small molecule or natural product SARS-CoV-2 Inhibition 7.3 pIC50 32
pIC50 7.3 (IC50 5x10-8 M) [32]
compound 15c [PMID: 34865476] Small molecule or natural product MERS-CoV Inhibition 7.3 pIC50 15
pIC50 7.3 (IC50 5x10-8 M) [15]
UAWJ9-36-3 Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 7.3 pIC50 45
pIC50 7.3 (IC50 5.4x10-8 M) [45]
compound 21 [Zhang et al., 2021] Small molecule or natural product SARS-CoV-2 Inhibition 7.2 pIC50 49
pIC50 7.2 (IC50 6.1x10-8 M) [49]
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 41
pIC50 7.2 (IC50 6.5x10-8 M) [41]
CCF981 Small molecule or natural product SARS-CoV-2 Inhibition 7.2 pIC50 20
pIC50 7.2 (IC50 6.8x10-8 M) [20]
GC-373 Peptide SARS-CoV Inhibition 7.2 pIC50 42
pIC50 7.2 (IC50 7x10-8 M) [42]
compound 19 [PMID: 35142215] Small molecule or natural product SARS-CoV-2 Inhibition 7.1 pIC50 27
pIC50 7.1 (IC50 7.7x10-8 M) [27]
Description: Inhibtion of protease activity
compound 2i [PMID: 23245752] Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 7.0 pIC50 41
pIC50 7.0 (IC50 9.4x10-8 M) [41]
UAWJ9-36-3 Small molecule or natural product Ligand has a PDB structure SARS-CoV Inhibition 7.0 pIC50 45
pIC50 7.0 (IC50 9.9x10-8 M) [45]
GC-376 Small molecule or natural product SARS-CoV-2 Inhibition 6.4 – 7.5 pIC50 16,27-28,42,45
pIC50 7.5 (IC50 3x10-8 M) [28]
pIC50 7.4 (IC50 4.1x10-8 M) [45]
pIC50 7.1 (IC50 7.3x10-8 M) [27]
pIC50 6.7 (IC50 1.9x10-7 M) [42]
pIC50 6.4 (IC50 4.1x10-7 M) [16]
GC-373 Peptide SARS-CoV-2 Inhibition 6.4 – 7.4 pIC50 41-42
pIC50 7.4 (IC50 4.2x10-8 M) [41]
pIC50 6.4 (IC50 4x10-7 M) [42]
compound 5 [Zhang et al., 2021] Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 6.8 pIC50 50
pIC50 6.8 (IC50 1.4x10-7 M) [50]
compound 6e [PMID: 32747425] Small molecule or natural product SARS-CoV-2 Inhibition 6.8 pIC50 34
pIC50 6.8 (IC50 1.7x10-7 M) [34]
compound 15c [PMID: 34865476] Small molecule or natural product SARS-CoV-2 Inhibition 6.8 pIC50 15
pIC50 6.8 (IC50 1.7x10-7 M) [15]
compound 1 [PMID: 34210738] Small molecule or natural product SARS-CoV-2 Inhibition 6.8 pIC50 16
pIC50 6.8 (IC50 1.7x10-7 M) [16]
compound 11r [PMID: 32045235] Small molecule or natural product SARS-CoV-2 Inhibition 6.7 pIC50 52
pIC50 6.7 (IC50 1.8x10-7 M) [52]
compound 2a [PMID: 34213885] Small molecule or natural product SARS-CoV-2 Inhibition 6.7 pIC50 13
pIC50 6.7 (IC50 1.8x10-7 M) [13]
Description: Determined in a FRET enzyme assay.
MAT-POS-932d1078-3 Small molecule or natural product SARS-CoV-2 Inhibition 6.7 pIC50 38
pIC50 6.7 (IC50 1.91x10-7 M) [38]
compound 10c [Dampalla et al., 2022] Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 6.6 pIC50 14
pIC50 6.6 (IC50 2.4x10-7 M) [14]
walrycin B Small molecule or natural product SARS-CoV-2 Inhibition 6.6 pIC50 55
pIC50 6.6 (IC50 2.6x10-7 M) [55]
Description: Inhibition determined in an HTS fluorogenic enzyme activity assay.
compound 3 [PMID: 16884309] Peptide SARS-CoV-2 Inhibition 6.5 pIC50 41
pIC50 6.5 (IC50 2.86x10-7 M) [41]
compound 10c [Dampalla et al., 2022] Small molecule or natural product Ligand has a PDB structure MERS-CoV Inhibition 6.5 pIC50 14
pIC50 6.5 (IC50 3.3x10-7 M) [14]
DAV-CRI-14a23e73-1 Small molecule or natural product SARS-CoV-2 Inhibition 6.3 pIC50 32
pIC50 6.3 (IC50 4.7x10-7 M) [32]
compound 6j [PMID: 32747425] Small molecule or natural product SARS-CoV-2 Inhibition 6.3 pIC50 34
pIC50 6.3 (IC50 4.8x10-7 M) [34]
compound 13b [PMID: 32198291] Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 6.2 pIC50 52
pIC50 6.2 (IC50 6.7x10-7 M) [52]
compound 6e [PMID: 32747425] Small molecule or natural product SARS-CoV Inhibition 6.1 pIC50 34
pIC50 6.1 (IC50 9x10-7 M) [34]
compound 6j [PMID: 32747425] Small molecule or natural product SARS-CoV Inhibition 5.9 pIC50 34
pIC50 5.9 (IC50 1.2x10-6 M) [34]
boceprevir Small molecule or natural product Approved drug SARS-CoV Inhibition 5.6 – 6.0 pIC50 1,4
pIC50 5.6 – 6.0 (IC50 2.5x10-6 – 9.49x10-7 M) [1,4]
compound 2i [PMID: 23245752] Small molecule or natural product Ligand has a PDB structure SARS-CoV Inhibition 5.8 pIC50 25
pIC50 5.8 (IC50 1.7x10-6 M) [25]
MG-132 Peptide Ligand has a PDB structure SARS-CoV-2 Inhibition 5.4 pIC50 28
pIC50 5.4 (IC50 3.9x10-6 M) [28]
boceprevir Small molecule or natural product Approved drug SARS-CoV-2 Inhibition 5.4 pIC50 28
pIC50 5.4 (IC50 4.13x10-6 M) [28]
ML300 Small molecule or natural product Ligand has a PDB structure SARS-CoV Inhibition 5.3 – 5.4 pIC50 20,39
pIC50 5.4 (IC50 4.1x10-6 M) [39]
pIC50 5.3 (IC50 4.45x10-6 M) [20]
compound 451 [WO2021252644A1] Small molecule or natural product SARS-CoV-2 Inhibition 5.0 – 5.7 pIC50 2
pIC50 5.0 – 5.7 (IC50 1x10-5 – 2x10-6 M) [2]
Description: In vitro inhibition of Mpro; binned IC50 value
ML300 Small molecule or natural product Ligand has a PDB structure SARS-CoV-2 Inhibition 5.3 pIC50 20
pIC50 5.3 (IC50 4.99x10-6 M) [20]
MG-115 Peptide SARS-CoV-2 Inhibition 5.2 pIC50 28
pIC50 5.2 (IC50 6.14x10-6 M) [28]
PRD_002214 Small molecule or natural product SARS-CoV Inhibition 5.1 pIC50 46
pIC50 5.1 (IC50 9x10-6 M) [46]
calpeptin Peptide SARS-CoV-2 Inhibition 5.0 pIC50 28
pIC50 5.0 (IC50 1.069x10-5 M) [28]
telaprevir Small molecule or natural product SARS-CoV-2 Inhibition 4.9 pIC50 31
pIC50 4.9 (IC50 1.147x10-5 M) [31]
Z-FA-FMK Peptide Immunopharmacology Ligand SARS-CoV-2 Inhibition 4.9 pIC50 55
pIC50 4.9 (IC50 1.139x10-5 M) [55]
Description: Inhibition determined in an HTS fluorogenic enzyme activity assay.
compound 25c [PMID: 23747811] Peptide SARS-CoV Inhibition 4.7 pIC50 37
pIC50 4.7 (IC50 2.1x10-5 M) [37]
PRD_002214 Small molecule or natural product SARS-CoV-2 Irreversible inhibition - - 23
[23]
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 [23].
The MERS-CoV inhibitor compound 11r [PMID: 32045235] is active against SARS-CoV-2 [51].
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 [4].
Chia et al. published a review of patents claiming coronavirus 3CLpro inhibitors in October 2021 [9].
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 45
pIC50 7.4 (IC50 4.1x10-8 M) [45]
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 [35].

Mpro has been reported to induce damage to the microvascular network in the brain, via proteolytic cleavage and inactivation of the endothelially-expressed protein NEMO (an essential NF-κB modulator with a central role in immunity; HGNC symbol IKBKG) [43]. Depletion of NEMO leads to cell death, and this cell death is dependent on receptor-interacting protein kinase 3 (RIPK3) signalling. A small molecule inhibitor of RIPK1, an upstream kinase that activates RIPK3, was shown to block the Mpro-induced microvascular pathology. It is interesting to note that a RIPK1 inhibitor (SAR443122) is already under clinical evaluation in COVID-19 patients.

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. Arnold LD, Jennings A, Keung W. (2021) Inhibitors of cysteine proteases and methods of use thereof. Patent number: WO2021252644A1. Assignee: Pardes Biosciences, Inc.. Priority date: 09/06/2020. Publication date: 16/12/2021.

3. 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]

4. 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]

5. 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.

6. 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]

7. 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]

8. Chen J, Liang C, Miao K, Wu Y, Yun H, Zhang W. (2022) Aminocarbamoyl compounds for the treatment of viral infections. Patent number: WO2022043374. Assignee: Hoffman La Roche. Priority date: 25/08/2021. Publication date: 03/03/2022.

9. Chia CSB, Xu W, Ng PS. (2021) A patent review on SARS coronavirus main protease (3CLpro) inhibitors. ChemMedChem, [Epub ahead of print]. DOI: 10.1002/cmdc.202100576 [PMID:34651447]

10. 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]

11. 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]

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