Title An orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations. Journal, issue, pages Sci Transl Med , Vol. 16, Page eadi0979-eadi0979, Year 2024Publish date Oct 1, 2021 (structure data deposition date) AuthorsWestberg, M. / Su, Y. / Zou, X. / Huang, P. / Rustagi, A. / Garhyan, J. / Patel, P.B. / Fernandez, D. / Wu, Y. / Hao, C. ...Westberg, M. / Su, Y. / Zou, X. / Huang, P. / Rustagi, A. / Garhyan, J. / Patel, P.B. / Fernandez, D. / Wu, Y. / Hao, C. / Lo, C.W. / Karim, M. / Ning, L. / Beck, A. / Saenkham-Huntsinger, P. / Tat, V. / Drelich, A. / Peng, B.H. / Einav, S. / Tseng, C.K. / Blish, C. / Lin, M.Z. External links Sci Transl Med / PubMed:38478629Methods X-ray diffraction Resolution 1.7 - 2 Å Structure data PDB-7set : Structure viewer SARS-CoV-2 Main Protease (Mpro) in Complex with ML1000 Method : X-RAY DIFFRACTION / Resolution : 1.7 Å
PDB-7sf1 : Structure viewer SARS-CoV-2 Main Protease (Mpro) in Complex with ML1001 Method : X-RAY DIFFRACTION / Resolution : 1.85 Å
PDB-7sf3 : Structure viewer SARS-CoV-2 Main Protease (Mpro) in Complex with ML1006m Method : X-RAY DIFFRACTION / Resolution : 1.75 Å
PDB-7u92 : Structure viewer SARS-CoV-2 Main Protease (Mpro) in Complex with ML1006a Method : X-RAY DIFFRACTION / Resolution : 1.8 Å
PDB-7uug : Structure viewer SARS-CoV-2 Main Protease S144A (Mpro S144A) in Complex with ML1006a Method : X-RAY DIFFRACTION / Resolution : 2 Å
PDB-7uup : Structure viewer SARS-CoV-2 Main Protease S144A (Mpro S144A) in Complex with Nirmatrelvir (PF-07321332) Method : X-RAY DIFFRACTION / Resolution : 2 Å
PDB-8ezv : Structure viewer SARS-CoV-2 Main Protease (Mpro) in Complex with ML2006a Method : X-RAY DIFFRACTION / Resolution : 1.8 Å
PDB-8ezz : Structure viewer SARS-CoV-2 Main Protease (Mpro) in Complex with ML2006a2 Method : X-RAY DIFFRACTION / Resolution : 1.85 Å
PDB-8f02 : Structure viewer SARS-CoV-2 Main Protease (Mpro) in Complex with ML2006a4 Method : X-RAY DIFFRACTION / Resolution : 2 Å
PDB-8f2c : Structure viewer SARS-CoV-2 Main Protease (Mpro) in Complex with ML3006a Method : X-RAY DIFFRACTION / Resolution : 1.95 Å
PDB-8f2d : Structure viewer SARS-CoV-2 Main Protease (Mpro) in Complex with ML4006a Method : X-RAY DIFFRACTION / Resolution : 1.95 Å
Chemicals ChemComp-I70 : Structure viewer (1R,2S,5S)-N-{(2S,3R)-4-amino-3-hydroxy-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}-3-[N-(tert-butylcarbamoyl)-3-methyl-L-valyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-8ZI : Structure viewer (1R,2S,5S)-N-{(2S,3R)-4-amino-3-hydroxy-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}-3-[N-(3,3-dimethylbutanoyl)-3-methyl-L-valyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-90H : Structure viewer (1R,2S,5S)-N-{(2S,3R)-3-hydroxy-4-(methylamino)-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-M0C : Structure viewer (1R,2S,5S)-N-{(2S,3R)-4-(azetidin-1-yl)-3-hydroxy-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-4WI : Structure viewer (1R,2S,5S)-N-{(1E,2S)-1-imino-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide / medication, antivirus, protease inhibitor*YM
ChemComp-X6O : Structure viewer (1R,2S,5S)-N-{(2S,3R)-4-(azetidin-1-yl)-3-hydroxy-4-oxo-1-[(3S)-2-oxopiperidin-3-yl]butan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-X70 : Structure viewer (1R,2S,5S)-N-{(2S,3R)-4-(3,3-difluoroazetidin-1-yl)-3-hydroxy-4-oxo-1-[(3S)-2-oxopiperidin-3-yl]butan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-X6T : Structure viewer (1R,2S,5S)-N-{(2S,3R)-4-(3,3-dimethylazetidin-1-yl)-3-hydroxy-4-oxo-1-[(3S)-2-oxopiperidin-3-yl]butan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-X9Z : Structure viewer (1R,2S,5S)-N-[(2S,3R)-4-(azetidin-1-yl)-3-hydroxy-4-oxo-1-(2-oxopyrrolidin-1-yl)butan-2-yl]-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-XA8 : Structure viewer (1R,2S,5S)-N-[(2S,3R)-4-(azetidin-1-yl)-3-hydroxy-4-oxo-1-(2-oxopiperidin-1-yl)butan-2-yl]-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
Source severe acute respiratory syndrome coronavirus 2 Keywords VIRAL PROTEIN / SARSCoV2 / SARS-CoV-2 / coronavirus / Main Protease / Protease / Mpro / 3C-like proteinase / CL3pro / Inhibitor / Complex / Covalent / Adduct / ML1000 / Ketoamide / Peptidomimetic / ML1001 / ML1006m / ML1006a / Azetidine / S144A / mutant / resistance / Nirmatrelvir / PF-07321332 / Nitrile / M2006a / M2006a2 / M2006a4 / M3006a / M4006a