Structure of PDB 8ifq Chain A Binding Site BS01

Receptor Information

>8ifq Chain A (length=305) Species: 2697049 (Severe acute respiratory syndrome coronavirus 2)

SGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDVVYCPRHVICTSEDML
NPNYEDLLIRKSNHNFLVQAGNVQLRVIGHSMQNCVLKLKVDTANPKTPK
YKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNFTIKGSFLNGSCGSVGF
NIDYDCVSFCYMHHMELPTGVHAGTDLEGNFYGPFVDRQTAQAAGTDTTI
TVNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLTQDHVDIL
GPLSAQTGIAVLDMCASLKELLQNGMNGRTILGSALLEDEFTPFDVVRQC
SGVTF

Ligand information

• Ligand ID: I1Z
• InChI: InChI=1S/C26H44N6O4/c1-24(2,3)19(30-23(36)31-25(4,5)6)22(35)32-13-16-17(26(16,7)8)18(32)21(34)29-15(12-27)11-14-9-10-28-20(14)33/h12,14-19,27H,9-11,13H2,1-8H3,(H,28,33)(H,29,34)(H2,30,31,36)/b27-12-/t14-,15-,16-,17-,18-,19+/m0/s1
• InChIKey: NJQHWGAQENWSGZ-CSXXOYNESA-N
• SMILES:
  OpenEye OEToolkits 2.0.7: CC1(C2C1C(N(C2)C(=O)C(C(C)(C)C)NC(=O)NC(C)(C)C)C(=O)NC(CC3CCNC3=O)C=N)C
  CACTVS 3.385: CC(C)(C)NC(=O)N[CH](C(=O)N1C[CH]2[CH]([CH]1C(=O)N[CH](C[CH]3CCNC3=O)C=N)C2(C)C)C(C)(C)C
  OpenEye OEToolkits 2.0.7: [H]/N=C\[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@@H]2[C@@H]3[C@@H](C3(C)C)CN2C(=O)[C@H](C(C)(C)C)NC(=O)NC(C)(C)C
  CACTVS 3.385: CC(C)(C)NC(=O)N[C@H](C(=O)N1C[C@H]2[C@@H]([C@H]1C(=O)N[C@@H](C[C@@H]3CCNC3=O)C=N)C2(C)C)C(C)(C)C
  ACDLabs 12.01: CC1(C)C2C(C(=O)NC(C=N)CC3CCNC3=O)N(CC21)C(=O)C(NC(=O)NC(C)(C)C)C(C)(C)C
• Formula: C26 H44 N6 O4
• Name: (1R,2S,5S)-3-[N-(tert-butylcarbamoyl)-3-methyl-L-valyl]-N-{(1Z,2S)-1-imino-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
• PDB chain: 8ifq Chain A Residue 401

Receptor-Ligand Complex Structure

Structure summary

• PDB: 8ifq Discovery of oral simnotrelvir, an approved SARS-CoV-2 3C-like protease inhibitor for the treatment of COVID-19
• Resolution: 1.96 Å
• Binding residue (original residue number in PDB): H41 F140 G143 C145 H163 H164 M165 E166 Q189 T190
• Binding residue (residue number reindexed from 1): H41 F140 G143 C145 H163 H164 M165 E166 Q189 T190
• Annotation score: 1

Enzymatic activity

• Enzyme Commision number: 2.1.1.56: mRNA (guanine-N(7))-methyltransferase.
  2.1.1.57: methyltransferase cap1.
  2.7.7.48: RNA-directed RNA polymerase.
  2.7.7.50: mRNA guanylyltransferase.
  3.1.13.-
  3.4.19.12: ubiquitinyl hydrolase 1.
  3.4.22.-
  3.4.22.69: SARS coronavirus main proteinase.
  3.6.4.12: DNA helicase.
  3.6.4.13: RNA helicase.
  4.6.1.-

Gene Ontology

Molecular Function

• GO:0008233 peptidase activity

Biological Process

• GO:0019082 viral protein processing

External links

• PDB: RCSB:8ifq, PDBe:8ifq, PDBj:8ifq
• PDBsum: 8ifq
• PubMed: 37833261
• UniProt: P0DTD1|R1AB_SARS2 Replicase polyprotein 1ab (Gene Name=rep)