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)-2-({N-[(benzyloxy)carbonyl]-L-leucyl}amino)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonic acid | Ligand Info | |||
| Canonical SMILES | CC(C)CC(C(=O)NC(CC1CCNC1=O)C(O)S(=O)(=O)O)NC(=O)OCC2=CC=CC=C2 | ||||
| InChI | 1S/C21H31N3O8S/c1-13(2)10-16(24-21(28)32-12-14-6-4-3-5-7-14)19(26)23-17(20(27)33(29,30)31)11-15-8-9-22-18(15)25/h3-7,13,15-17,20,27H,8-12H2,1-2H3,(H,22,25)(H,23,26)(H,24,28)(H,29,30,31)/t15-,16-,17-,20+/m0/s1 | ||||
| InChIKey | BSPZFJDYQHDZNR-OGNFBWPZSA-N | ||||
| PubChem Compound ID | 137348969 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 7CB7 1.7A resolution structure of SARS-CoV-2 main protease (Mpro) in complex with broad-spectrum coronavirus protease inhibitor GC376 | ||||||
| Method | X-ray diffraction | Resolution | 1.69 Å | Mutation | No | [1] |
| PDB Sequence |
GSGGGSGFRK
5 MAFPSGKVEG15 CMVQVTCGTT25 TLNGLWLDDV35 VYCPRHVICT45 SEDMLNPNYE 55 DLLIRKSNHN65 FLVQAGNVQL75 RVIGHSMQNC85 VLKLKVDTAN95 PKTPKYKFVR 105 IQPGQTFSVL115 ACYNGSPSGV125 YQCAMRPNFT135 IKGSFLNGSC145 GSVGFNIDYD 155 CVSFCYMHHM165 ELPTGVHAGT175 DLEGNFYGPF185 VDRQTAQAAG195 TDTTITVNVL 205 AWLYAAVING215 DRWFLNRFTT225 TLNDFNLVAM235 KYNYEPLTQD245 HVDILGPLSA 255 QTGIAVLDMC265 ASLKELLQNG275 MNGRTILGSA285 LLEDEFTPFD295 VVRQCSG |
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THR26
4.895
LEU27
3.734
HIS41
2.693
MET49
2.787
TYR54
3.595
PHE140
2.534
LEU141
3.081
ASN142
2.738
GLY143
3.694
SER144
3.261
CYS145
1.769
|
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| PDB ID: 8DD9 Crystal Structure of SARS-CoV-2 Main Protease (Mpro) S144L Mutant in Complex with Inhibitor GC376 | ||||||
| Method | X-ray diffraction | Resolution | 2.04 Å | Mutation | Yes | [2] |
| PDB Sequence |
SGFRKMAFPS
10 GKVEGCMVQV20 TCGTTTLNGL30 WLDDVVYCPR40 HVICTSEDML50 NPNYEDLLIR 60 KSNHNFLVQA70 GNVQLRVIGH80 SMQNCVLKLK90 VDTANPKTPK100 YKFVRIQPGQ 110 TFSVLACYNG120 SPSGVYQCAM130 RPNFTIKGSF140 LNGLCGSVGF150 NIDYDCVSFC 160 YMHHMELPTG170 VHAGTDLEGN180 FYGPFVDRQT190 AQAAGTDTTI200 TVNVLAWLYA 210 AVINGDRWFL220 NRFTTTLNDF230 NLVAMKYNYE240 PLTQDHVDIL250 GPLSAQTGIA 260 VLDMCASLKE270 LLQNGMNGRT280 ILGSALLEDE290 FTPFDVVRQC300 SGVT |
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| PDB ID: 8DGB Crystal Structure of SARS-CoV-2 Main Protease (Mpro) Q192T Mutant in Complex with Inhibitor GC376 | ||||||
| Method | X-ray diffraction | Resolution | 2.87 Å | Mutation | Yes | [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 ATAAGTDTTI200 TVNVLAWLYA 210 AVINGDRWFL220 NRFTTTLNDF230 NLVAMKYNYE240 PLTQDHVDIL250 GPLSAQTGIA 260 VLDMCASLKE270 LLQNGMNGRT280 ILGSALLEDE290 FTPFDVVRQC300 SGVT |
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LEU27
4.863
HIS41
3.174
MET49
3.916
TYR54
4.287
PHE140
3.392
LEU141
3.620
ASN142
3.219
GLY143
4.162
SER144
4.095
CYS145
1.844
HIS163
2.653
|
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| PDB ID: 7TGR Structure of SARS-CoV-2 main protease in complex with GC376 | ||||||
| Method | X-ray diffraction | Resolution | 1.68 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 SGVT |
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Click to Show 3D Structure of This Binding Site
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structural basis of SARS-CoV-2 main protease inhibition by a broad-spectrum anti-coronaviral drug. Am J Cancer Res. 2020 Aug 1;10(8):2535-2545. eCollection 2020. | ||||
| REF 2 | Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir. bioRxiv. 2022 Sep 6:2022.06.28.497978. | ||||
| REF 3 | Gain-of-Signal Assays for Probing Inhibition of SARS-CoV-2 M(pro)/3CL(pro) in Living Cells. mBio. 2022 Jun 28;13(3):e0078422. | ||||
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