7RC1
X-ray Structure of SARS-CoV main protease covalently modified by compound GRL-0686
Summary for 7RC1
| Entry DOI | 10.2210/pdb7rc1/pdb |
| Descriptor | 3C-like proteinase, 5-chloropyridin-3-yl 1-(3-nitrobenzene-1-sulfonyl)-1H-indole-5-carboxylate, DIMETHYL SULFOXIDE, ... (4 entities in total) |
| Functional Keywords | sars-cov, 3clpro, mpro, 3cl, main, protease, inhibitor, covalent, structural genomics, center for structural genomics of infectious diseases, csgid, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus (SARS-CoV) |
| Total number of polymer chains | 1 |
| Total formula weight | 34725.15 |
| Authors | Mesecar, A.D.,Anson, B.A.,Ghosh, A.K.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2021-07-07, release date: 2021-09-29, Last modification date: 2024-10-23) |
| Primary citation | Ghosh, A.K.,Raghavaiah, J.,Shahabi, D.,Yadav, M.,Anson, B.J.,Lendy, E.K.,Hattori, S.I.,Higashi-Kuwata, N.,Mitsuya, H.,Mesecar, A.D. Indole Chloropyridinyl Ester-Derived SARS-CoV-2 3CLpro Inhibitors: Enzyme Inhibition, Antiviral Efficacy, Structure-Activity Relationship, and X-ray Structural Studies. J.Med.Chem., 64:14702-14714, 2021 Cited by PubMed Abstract: Here, we report the synthesis, structure-activity relationship studies, enzyme inhibition, antiviral activity, and X-ray crystallographic studies of 5-chloropyridinyl indole carboxylate derivatives as a potent class of SARS-CoV-2 chymotrypsin-like protease inhibitors. Compound exhibited a SARS-CoV-2 3CLpro inhibitory IC value of 250 nM and an antiviral EC value of 2.8 μM in VeroE6 cells. Remdesivir, an RNA-dependent RNA polymerase inhibitor, showed an antiviral EC value of 1.2 μM in the same assay. Compound showed comparable antiviral activity with remdesivir in immunocytochemistry assays. Compound with an -allyl derivative showed the most potent enzyme inhibitory IC value of 73 nM. To obtain molecular insight into the binding properties of these molecules, X-ray crystal structures of compounds , , and -bound to SARS-CoV 3CLpro were determined, and their binding properties were compared. PubMed: 34528437DOI: 10.1021/acs.jmedchem.1c01214 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.63 Å) |
Structure validation
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