Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T88015 | Target Info | |||
| Target 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 | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | (1s,3ar,6as)-2-[(2s)-2-({(2s)-2-Cyclohexyl-2-[(Pyrazin-2-Ylcarbonyl)amino]acetyl}amino)-3,3-Dimethylbutanoyl]-N-[(2r,3s)-1-(Cyclopropylamino)-2-Hydroxy-1-Oxohexan-3-Yl]octahydrocyclopenta[c]pyrrole-1-Carboxamide | Ligand Info | |||
| Canonical SMILES | CCCC(C(C(=O)NC1CC1)O)NC(=O)C2C3CCCC3CN2C(=O)C(C(C)(C)C)NC(=O)C(C4CCCCC4)NC(=O)C5=NC=CN=C5 | ||||
| InChI | 1S/C36H55N7O6/c1-5-10-25(29(44)34(48)39-23-15-16-23)40-33(47)28-24-14-9-13-22(24)20-43(28)35(49)30(36(2,3)4)42-32(46)27(21-11-7-6-8-12-21)41-31(45)26-19-37-17-18-38-26/h17-19,21-25,27-30,44H,5-16,20H2,1-4H3,(H,39,48)(H,40,47)(H,41,45)(H,42,46)/t22-,24-,25-,27-,28-,29+,30+/m0/s1 | ||||
| InChIKey | FTZGWEAUHOMNIG-FJRGXGLZSA-N | ||||
| PubChem Compound ID | 59235547 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 7K6D SARS-CoV-2 Main Protease Co-Crystal Structure with Telaprevir Determined from Crystals Grown with 40 nL Acoustically Ejected Mpro Droplets at 1.48 A Resolution (Cryo-protected) | ||||||
| Method | X-ray diffraction | Resolution | 1.48 Å | Mutation | No | [1] |
| PDB Sequence |
SGFRKMAFPS
10 GKVEGCMVQV20 TCGTTTLNGL30 WLDDVVYCPR40 HVICTSEDML50 NPNYEDLLIR 60 KSNHNFLVQA70 GNVQLRVIGH80 SMQNCVLKLK90 VDTANPKTPK100 YKFVRIQPGQ 110 TFSVLACYNG120 SPSGVYQCAM130 RPNFTIKGSF140 LNGSCGSVGF150 NIDYDCVSFC 160 YMHHMELPTG170 VHAGTDLEGN180 FYGPFVDRQT190 AQAAGTDTTI200 TVNVLAWLYA 210 AVINGDRWFL220 NRFTTTLNDF230 NLVAMKYNYE240 PLTQDHVDIL250 GPLSAQTGIA 260 VLDMCASLKE270 LLQNGMNGRT280 ILGSALLEDE290 FTPFDVVRQC300 SGVTF |
|||||
|
|
THR25
3.979
THR26
3.209
LEU27
4.034
HIS41
2.494
MET49
3.332
LEU141
4.453
ASN142
3.673
GLY143
2.892
SER144
3.241
CYS145
1.779
HIS163
4.240
HIS164
3.020
|
|||||
| PDB ID: 7K6E SARS-CoV-2 Main Protease Co-Crystal Structure with Telaprevir Determined from Crystals Grown with 40 nL Acoustically Ejected Mpro Droplets at 1.63 A Resolution (Direct Vitrification) | ||||||
| Method | X-ray diffraction | Resolution | 1.63 Å | Mutation | No | [1] |
| PDB Sequence |
SGFRKMAFPS
10 GKVEGCMVQV20 TCGTTTLNGL30 WLDDVVYCPR40 HVICTSEDML50 NPNYEDLLIR 60 KSNHNFLVQA70 GNVQLRVIGH80 SMQNCVLKLK90 VDTANPKTPK100 YKFVRIQPGQ 110 TFSVLACYNG120 SPSGVYQCAM130 RPNFTIKGSF140 LNGSCGSVGF150 NIDYDCVSFC 160 YMHHMELPTG170 VHAGTDLEGN180 FYGPFVDRQT190 AQAAGTDTTI200 TVNVLAWLYA 210 AVINGDRWFL220 NRFTTTLNDF230 NLVAMKYNYE240 PLTQDHVDIL250 GPLSAQTGIA 260 VLDMCASLKE270 LLQNGMNGRT280 ILGSALLEDE290 FTPFDVVRQC300 SGVTF |
|||||
|
|
THR25
3.968
THR26
3.212
LEU27
4.054
HIS41
2.466
MET49
4.114
LEU141
4.424
ASN142
3.220
GLY143
2.949
SER144
3.258
CYS145
1.792
HIS164
3.029
MET165
3.290
|
|||||
| PDB ID: 7C7P Crystal structure of the SARS-CoV-2 main protease in complex with Telaprevir | ||||||
| Method | X-ray diffraction | Resolution | 1.74 Å | Mutation | No | [2] |
| PDB Sequence |
SGFRKMAFPS
10 GKVEGCMVQV20 TCGTTTLNGL30 WLDDVVYCPR40 HVICTSEDML50 NPNYEDLLIR 60 KSNHNFLVQA70 GNVQLRVIGH80 SMQNCVLKLK90 VDTANPKTPK100 YKFVRIQPGQ 110 TFSVLACYNG120 SPSGVYQCAM130 RPNFTIKGSF140 LNGSCGSVGF150 NIDYDCVSFC 160 YMHHMELPTG170 VHAGTDLEGN180 FYGPFVDRQT190 AQAAGTDTTI200 TVNVLAWLYA 210 AVINGDRWFL220 NRFTTTLNDF230 NLVAMKYNYE240 PLTQDHVDIL250 GPLSAQTGIA 260 VLDMCASLKE270 LLQNGMNGRT280 ILGSALLEDE290 FTPFDVVRQC300 S |
|||||
|
|
THR25
3.947
THR26
3.127
LEU27
4.138
HIS41
2.436
MET49
3.497
LEU141
4.388
ASN142
3.366
GLY143
2.892
SER144
3.223
CYS145
1.817
HIS163
4.998
HIS164
3.071
|
|||||
| PDB ID: 6XQS Room-temperature X-ray Crystal structure of SARS-CoV-2 main protease in complex with Telaprevir | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [3] |
| PDB Sequence |
SGFRKMAFPS
10 GKVEGCMVQV20 TCGTTTLNGL30 WLDDVVYCPR40 HVICTSEDML50 NPNYEDLLIR 60 KSNHNFLVQA70 GNVQLRVIGH80 SMQNCVLKLK90 VDTANPKTPK100 YKFVRIQPGQ 110 TFSVLACYNG120 SPSGVYQCAM130 RPNFTIKGSF140 LNGSCGSVGF150 NIDYDCVSFC 160 YMHHMELPTG170 VHAGTDLEGN180 FYGPFVDRQT190 AQAAGTDTTI200 TVNVLAWLYA 210 AVINGDRWFL220 NRFTTTLNDF230 NLVAMKYNYE240 PLTQDHVDIL250 GPLSAQTGIA 260 VLDMCASLKE270 LLQNGMNGRT280 ILGSALLEDE290 FTPFDVVRQC300 SGVTFQ |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SV6 or .SV62 or .SV63 or :3SV6;style chemicals stick;color identity;select .A:25 or .A:26 or .A:27 or .A:41 or .A:49 or .A:141 or .A:142 or .A:143 or .A:144 or .A:145 or .A:164 or .A:165 or .A:166 or .A:167 or .A:168 or .A:185 or .A:186 or .A:187 or .A:188 or .A:189 or .A:190 or .A:191 or .A:192; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
THR25
4.045
THR26
3.305
LEU27
3.925
HIS41
2.527
MET49
3.882
LEU141
4.545
ASN142
3.300
GLY143
2.877
SER144
3.266
CYS145
1.861
HIS164
2.965
MET165
3.298
|
|||||
| PDB ID: 7LB7 Joint X-ray/neutron structure of SARS-CoV-2 main protease (3CL Mpro) in complex with Telaprevir | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [4] |
| PDB Sequence |
SGFRKMAFPS
10 GKVEGCMVQV20 TCGTTTLNGL30 WLDDVVYCPR40 HVICTSEDML50 NPNYEDLLIR 60 KSNHNFLVQA70 GNVQLRVIGH80 SMQNCVLKLK90 VDTANPKTPK100 YKFVRIQPGQ 110 TFSVLACYNG120 SPSGVYQCAM130 RPNFTIKGSF140 LNGSCGSVGF150 NIDYDCVSFC 160 YMHHMELPTG170 VHAGTDLEGN180 FYGPFVDRQT190 AQAAGTDTTI200 TVNVLAWLYA 210 AVINGDRWFL220 NRFTTTLNDF230 NLVAMKYNYE240 PLTQDHVDIL250 GPLSAQTGIA 260 VLDMCASLKE270 LLQNGMNGRT280 ILGSALLEDE290 FTPFDVVRQC300 SGVTFQ |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SV6 or .SV62 or .SV63 or :3SV6;style chemicals stick;color identity;select .A:25 or .A:26 or .A:27 or .A:39 or .A:41 or .A:49 or .A:54 or .A:140 or .A:141 or .A:142 or .A:143 or .A:144 or .A:145 or .A:163 or .A:164 or .A:165 or .A:166 or .A:167 or .A:168 or .A:173 or .A:181 or .A:185 or .A:186 or .A:187 or .A:188 or .A:189 or .A:190 or .A:191 or .A:192 or .A:193; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
THR25
2.861
THR26
2.756
LEU27
2.975
PRO39
4.914
HIS41
1.857
MET49
2.906
TYR54
4.100
PHE140
4.935
LEU141
3.300
ASN142
2.363
GLY143
2.076
SER144
2.910
CYS145
1.855
HIS163
3.548
HIS164
2.158
|
|||||
| PDB ID: 6ZRT Crystal structure of SARS CoV2 main protease in complex with inhibitor Telaprevir | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [5] |
| PDB Sequence |
SGFRKMAFPS
10 GKVEGCMVQV20 TCGTTTLNGL30 WLDDVVYCPR40 HVICTSEDML50 NPNYEDLLIR 60 KSNHNFLVQA70 GNVQLRVIGH80 SMQNCVLKLK90 VDTANPKTPK100 YKFVRIQPGQ 110 TFSVLACYNG120 SPSGVYQCAM130 RPNFTIKGSF140 LNGSCGSVGF150 NIDYDCVSFC 160 YMHHMELPTG170 VHAGTDLEGN180 FYGPFVDRQT190 AQAAGTDTTI200 TVNVLAWLYA 210 AVINGDRWFL220 NRFTTTLNDF230 NLVAMKYNYE240 PLTQDHVDIL250 GPLSAQTGIA 260 VLDMCASLKE270 LLQNGMNGRT280 ILGSALLEDE290 FTPFDVVRQC300 SGVT |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SV6 or .SV62 or .SV63 or :3SV6;style chemicals stick;color identity;select .A:25 or .A:26 or .A:27 or .A:41 or .A:49 or .A:140 or .A:141 or .A:142 or .A:143 or .A:144 or .A:145 or .A:163 or .A:164 or .A:165 or .A:166 or .A:167 or .A:168 or .A:172 or .A:185 or .A:186 or .A:187 or .A:188 or .A:189 or .A:190 or .A:191 or .A:192; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
THR25
4.206
THR26
3.439
LEU27
4.248
HIS41
2.587
MET49
3.919
PHE140
4.334
LEU141
4.048
ASN142
3.549
GLY143
2.784
SER144
3.255
CYS145
1.805
HIS163
3.604
HIS164
3.077
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Hepatitis C virus NS3/4A inhibitors and other drug-like compounds as covalent binders of SARS-CoV-2 main protease. Sci Rep. 2022 Jul 16;12(1):12197. | ||||
| REF 2 | SARS-CoV-2 M(pro) inhibitors with antiviral activity in a transgenic mouse model. Science. 2021 Mar 26;371(6536):1374-1378. | ||||
| REF 3 | Malleability of the SARS-CoV-2 3CL M(pro) Active-Site Cavity Facilitates Binding of Clinical Antivirals. Structure. 2020 Dec 1;28(12):1313-1320.e3. | ||||
| REF 4 | Direct Observation of Protonation State Modulation in SARS-CoV-2 Main Protease upon Inhibitor Binding with Neutron Crystallography. J Med Chem. 2021 Apr 22;64(8):4991-5000. | ||||
| REF 5 | Repurposing the HCV NS3-4A protease drug boceprevir as COVID-19 therapeutics. RSC Med Chem. 2020 Dec 21;12(3):370-379. | ||||
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