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 | (1R,2S,5S)-N-[(2S,3R)-4-amino-1-cyclobutyl-3-hydroxy-4-oxobutan-2-yl]-3-[(2S)-2-(tert-butylcarbamoylamino)-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide | Ligand Info | |||
| Canonical SMILES | CC1(C2C1C(N(C2)C(=O)C(C(C)(C)C)NC(=O)NC(C)(C)C)C(=O)NC(CC3CCC3)C(C(=O)N)O)C | ||||
| InChI | 1S/C27H47N5O5/c1-25(2,3)20(30-24(37)31-26(4,5)6)23(36)32-13-15-17(27(15,7)8)18(32)22(35)29-16(19(33)21(28)34)12-14-10-9-11-14/h14-20,33H,9-13H2,1-8H3,(H2,28,34)(H,29,35)(H2,30,31,37)/t15-,16-,17-,18-,19+,20+/m0/s1 | ||||
| InChIKey | FEBWCINGHXXUCV-GFLQDLJJSA-N | ||||
| PubChem Compound ID | 71316139 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 7BRP Crystal structure of the 2019-nCoV main protease complexed with Boceprevir | ||||||
| Method | X-ray diffraction | Resolution | 1.80 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 S |
|||||
|
|
THR26
4.460
LEU27
4.255
HIS41
2.584
MET49
3.275
TYR54
3.992
PHE140
4.961
LEU141
3.996
ASN142
3.309
GLY143
2.794
SER144
3.172
CYS145
1.860
HIS164
2.905
|
|||||
| PDB ID: 7K40 Crystal Structure of SARS-CoV-2 Main Protease (3CLpro/Mpro) in Complex with Covalent Inhibitor Boceprevir at 1.35 A Resolution | ||||||
| Method | X-ray diffraction | Resolution | 1.35 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 SGVTFQ |
|||||
|
|
THR26
4.667
LEU27
4.559
HIS41
2.509
MET49
3.696
TYR54
3.708
PHE140
4.378
LEU141
3.969
ASN142
3.572
GLY143
2.806
SER144
3.147
CYS145
1.912
HIS163
4.743
|
|||||
| PDB ID: 6WNP X-ray Structure of SARS-CoV-2 main protease bound to Boceprevir at 1.45 A | ||||||
| Method | X-ray diffraction | Resolution | 1.44 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 |
|||||
|
|
THR25
3.747
THR26
3.269
LEU27
2.344
PRO39
4.631
HIS41
2.525
CYS44
4.652
MET49
2.403
PRO52
4.377
TYR54
3.375
PHE140
4.888
LEU141
3.435
ASN142
2.410
GLY143
2.101
SER144
2.873
CYS145
1.805
|
|||||
| PDB ID: 7C6S Crystal structure of the SARS-CoV-2 main protease complexed with Boceprevir | ||||||
| Method | X-ray diffraction | Resolution | 1.60 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 S |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .U5G or .U5G2 or .U5G3 or :3U5G;style chemicals stick;color identity;select .A:26 or .A:27 or .A:41 or .A:49 or .A:54 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: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
|
THR26
3.750
LEU27
3.942
HIS41
2.542
MET49
3.566
TYR54
3.823
LEU141
4.206
ASN142
3.518
GLY143
2.781
SER144
3.071
CYS145
1.766
HIS164
3.034
|
|||||
| PDB ID: 6ZRU Crystal structure of SARS CoV2 main protease in complex with inhibitor Boceprevir | ||||||
| Method | X-ray diffraction | Resolution | 2.10 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 SGVT |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .U5G or .U5G2 or .U5G3 or :3U5G;style chemicals stick;color identity;select .A:25 or .A:26 or .A:27 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:186 or .A:187 or .A:188 or .A:189 or .A:190 or .A:191 or .A:192; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
THR25
4.968
THR26
4.587
LEU27
4.523
HIS41
2.568
MET49
3.575
TYR54
3.820
PHE140
4.278
LEU141
4.105
ASN142
3.746
GLY143
2.923
SER144
3.099
CYS145
1.826
HIS163
4.603
|
|||||
| PDB ID: 6XQU Room-temperature X-ray Crystal structure of SARS-CoV-2 main protease in complex with Boceprevir | ||||||
| Method | X-ray diffraction | Resolution | 2.20 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 SGVTFQ |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .U5G or .U5G2 or .U5G3 or :3U5G;style chemicals stick;color identity;select .A:25 or .A:26 or .A:27 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: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
4.681
THR26
4.379
LEU27
4.385
HIS41
2.418
MET49
3.754
TYR54
3.929
PHE140
4.404
LEU141
3.724
ASN142
3.671
GLY143
2.783
SER144
3.301
CYS145
1.827
HIS163
3.878
|
|||||
| PDB ID: 7COM Crystal structure of the SARS-CoV-2 main protease in complex with Boceprevir (space group P212121) | ||||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | No | [6] |
| 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 |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .U5G or .U5G2 or .U5G3 or :3U5G;style chemicals stick;color identity;select .A:25 or .A:26 or .A:27 or .A:41 or .A:49 or .A:54 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:186 or .A:187 or .A:188 or .A:189 or .A:190 or .A:191 or .A:192; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
THR25
4.825
THR26
4.114
LEU27
3.862
HIS41
2.457
MET49
3.812
TYR54
4.144
LEU141
4.199
ASN142
3.597
GLY143
2.913
SER144
3.215
CYS145
1.861
HIS163
4.899
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease. Nat Commun. 2020 Sep 4;11(1):4417. | ||||
| REF 2 | 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 3 | X-ray Structure of SARS-CoV-2 main protease bound to Boceprevir at 1.45 A | ||||
| REF 4 | Repurposing the HCV NS3-4A protease drug boceprevir as COVID-19 therapeutics. RSC Med Chem. 2020 Dec 21;12(3):370-379. | ||||
| REF 5 | 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 6 | SARS-CoV-2 M(pro) inhibitors with antiviral activity in a transgenic mouse model. Science. 2021 Mar 26;371(6536):1374-1378. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.