6XR3
X-ray Structure of SARS-CoV-2 main protease bound to GRL-024-20 at 1.45 A
Summary for 6XR3
| Entry DOI | 10.2210/pdb6xr3/pdb |
| Related | 6W63 6WNP |
| Descriptor | 3C-like proteinase, N-[(2S)-1-({(1S,2S)-1-(1,3-benzothiazol-2-yl)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}amino)-4-methyl-1-oxopentan-2-yl]-4-methoxy-1H-indole-2-carboxamide (3 entities in total) |
| Functional Keywords | inhibitor, main protease, mpro, 3c-like, 3clpro, sars-cov-2, covid-19, nsp5, structural genomics, center for structural genomics of infectious diseases, csgid, hydrolase |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) |
| Total number of polymer chains | 1 |
| Total formula weight | 34403.24 |
| Authors | Anson, B.,Ghosh, A.K.,Mesecar, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2020-07-10, release date: 2020-08-19, Last modification date: 2026-04-22) |
| Primary citation | Hattori, S.I.,Higashi-Kuwata, N.,Hayashi, H.,Allu, S.R.,Raghavaiah, J.,Bulut, H.,Das, D.,Anson, B.J.,Lendy, E.K.,Takamatsu, Y.,Takamune, N.,Kishimoto, N.,Murayama, K.,Hasegawa, K.,Li, M.,Davis, D.A.,Kodama, E.N.,Yarchoan, R.,Wlodawer, A.,Misumi, S.,Mesecar, A.D.,Ghosh, A.K.,Mitsuya, H. A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication. Nat Commun, 12:668-668, 2021 Cited by PubMed Abstract: Except remdesivir, no specific antivirals for SARS-CoV-2 infection are currently available. Here, we characterize two small-molecule-compounds, named GRL-1720 and 5h, containing an indoline and indole moiety, respectively, which target the SARS-CoV-2 main protease (M). We use VeroE6 cell-based assays with RNA-qPCR, cytopathic assays, and immunocytochemistry and show both compounds to block the infectivity of SARS-CoV-2 with EC values of 15 ± 4 and 4.2 ± 0.7 μM for GRL-1720 and 5h, respectively. Remdesivir permitted viral breakthrough at high concentrations; however, compound 5h completely blocks SARS-CoV-2 infection in vitro without viral breakthrough or detectable cytotoxicity. Combination of 5h and remdesivir exhibits synergism against SARS-CoV-2. Additional X-ray structural analysis show that 5h forms a covalent bond with M and makes polar interactions with multiple active site amino acid residues. The present data suggest that 5h might serve as a lead M inhibitor for the development of therapeutics for SARS-CoV-2 infection. PubMed: 33510133DOI: 10.1038/s41467-021-20900-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.45 Å) |
Structure validation
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