8HBL
Crystal structure of the SARS-unique domain (SUD) of SARS-CoV-2 (1.58 angstrom resolution)
Summary for 8HBL
| Entry DOI | 10.2210/pdb8hbl/pdb |
| Descriptor | Non-structural protein 3, PHOSPHATE ION, LITHIUM ION, ... (5 entities in total) |
| Functional Keywords | nsp3, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 |
| Total number of polymer chains | 1 |
| Total formula weight | 29050.09 |
| Authors | Qin, B.,Li, Z.,Aumonier, S.,Wang, M.,Cui, S. (deposition date: 2022-10-29, release date: 2023-07-12, Last modification date: 2024-10-30) |
| Primary citation | Qin, B.,Li, Z.,Tang, K.,Wang, T.,Xie, Y.,Aumonier, S.,Wang, M.,Yuan, S.,Cui, S. Identification of the SARS-unique domain of SARS-CoV-2 as an antiviral target. Nat Commun, 14:3999-3999, 2023 Cited by PubMed Abstract: SARS-CoV-2 nsp3 is essential for viral replication and host responses. The SARS-unique domain (SUD) of nsp3 exerts its function through binding to viral and host proteins and RNAs. Herein, we show that SARS-CoV-2 SUD is highly flexible in solution. The intramolecular disulfide bond of SARS-CoV SUD is absent in SARS-CoV-2 SUD. Incorporating this bond in SARS-CoV-2 SUD allowed crystal structure determination to 1.35 Å resolution. However, introducing this bond in SARS-CoV-2 genome was lethal for the virus. Using biolayer interferometry, we screened compounds directly binding to SARS-CoV-2 SUD and identified theaflavin 3,3'-digallate (TF3) as a potent binder, K 2.8 µM. TF3 disrupted the SUD-guanine quadruplex interactions and exhibited anti-SARS-CoV-2 activity in Vero E6-TMPRSS2 cells with an EC of 5.9 µM and CC of 98.5 µM. In this work, we provide evidence that SARS-CoV-2 SUD harbors druggable sites for antiviral development. PubMed: 37414753DOI: 10.1038/s41467-023-39709-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.58 Å) |
Structure validation
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