8UND
X-ray Structure of SARS-CoV-2 main protease covalently bound to inhibitor GRL-190-21 at 1.90 A.
Summary for 8UND
| Entry DOI | 10.2210/pdb8und/pdb |
| Descriptor | ORF1a polyprotein, (1R,2S,5S)-N-{(1E,2S)-1-imino-3-[(3S)-2-oxopiperidin-3-yl]propan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide (3 entities in total) |
| Functional Keywords | main protease, 3c like protease, 3clpro, mpro, nirmatrelvir, inhibitor, covid-19, sars-cov-2, structural genomics, center for structural biology of infectious diseases, csbid, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus |
| Total number of polymer chains | 1 |
| Total formula weight | 34341.12 |
| Authors | Mesecar, A.D.,Lendy, E.K.,Ghosh, A.K.,Center for Structural Biology of Infectious Diseases (CSBID) (deposition date: 2023-10-18, release date: 2024-10-23, Last modification date: 2026-03-25) |
| Primary citation | Ghosh, A.K.,Yadav, M.,Iddum, S.,Ghazi, S.,Lendy, E.K.,Jayashankar, U.,Beechboard, S.N.,Takamatsu, Y.,Hattori, S.I.,Amano, M.,Higashi-Kuwata, N.,Mitsuya, H.,Mesecar, A.D. Exploration of P1 and P4 modifications of nirmatrelvir: Design, synthesis, biological evaluation, and X-ray structural studies of SARS-CoV-2 Mpro inhibitors. Eur.J.Med.Chem., 267:116132-116132, 2024 Cited by PubMed Abstract: We report the synthesis, biological evaluation, and X-ray structural studies of a series of SARS-CoV-2 Mpro inhibitors based upon the X-ray crystal structure of nirmatrelvir, an FDA approved drug that targets the main protease of SARS-CoV-2. The studies involved examination of various P4 moieties, P1 five- and six-membered lactam rings to improve potency. In particular, the six-membered P1 lactam ring analogs exhibited high SARS-CoV-2 Mpro inhibitory activity. Several compounds effectively blocked SARS-CoV-2 replication in VeroE6 cells. One of these compounds maintained good antiviral activity against variants of concern including Delta and Omicron variants. A high-resolution X-ray crystal structure of an inhibitor bound to SARS-CoV-2 Mpro was determined to gain insight into the ligand-binding properties in the Mpro active site. PubMed: 38335815DOI: 10.1016/j.ejmech.2024.116132 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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