9NFP
Structure of SARS-CoV-2 NSP14 bound to N-((4-cyclopropylthiazol-2-yl)methyl)-1H-pyrazole-3-carboxamide
This is a non-PDB format compatible entry.
Summary for 9NFP
| Entry DOI | 10.2210/pdb9nfp/pdb |
| Related | 9NAZ |
| Descriptor | Guanine-N7 methyltransferase nsp14, ZINC ION, PHOSPHATE ION, ... (5 entities in total) |
| Functional Keywords | nsp14, exonuclease, fragment, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 |
| Total number of polymer chains | 1 |
| Total formula weight | 60168.64 |
| Authors | Coker, J.A.,Sun, R.,Polzer, P.M.,Jung, J.,Stauffer, S.R. (deposition date: 2025-02-21, release date: 2025-12-03, Last modification date: 2026-03-04) |
| Primary citation | Coker, J.A.,Sun, R.,Polzer, P.M.,Romigh, T.,Goins, C.M.,Wang, N.S.,Jung, J.U.,Stauffer, S.R. Fragment-Based Development of NSP14 Exonuclease Inhibitors Confounded by Batch-to-Batch Variability. Acs Chem.Biol., 2026 Cited by PubMed Abstract: Point mutations in the exonuclease (ExoN) site of nonstructural protein 14 (NSP14) compromise the fitness of betacoronaviruses such as SARS-CoV-2, implicating NSP14 ExoN inhibition as an antiviral strategy. However, there are no advanced compounds that inhibit NSP14's ExoN activity. Building upon the reported crystal structures of two fragments bound to NSP14's ExoN site, we identified a series of 3,5-disubsituted pyrazoles that bound to and inhibited NSP14 ExoN. However, upon resynthesis, we discovered that these putative leads were false positives, perhaps due to contaminating divalent cations, which potently inhibit NSP14 ExoN. Our results provide a cautionary tale to the field about the sensitivity of NSP14 to divalent cations and illustrate the challenges associated with directly targeting the NSP14 ExoN site via fragment merging. PubMed: 41698876DOI: 10.1021/acschembio.5c00930 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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