7ULT
Crystal Structure of SARS-CoV-2 Nsp16/10 Heterodimer Apo-Form.
Summary for 7ULT
| Entry DOI | 10.2210/pdb7ult/pdb |
| Descriptor | 2'-O-methyltransferase, Non-structural protein 10, SODIUM ION, ... (6 entities in total) |
| Functional Keywords | structural genomics, center for structural genomics of infectious diseases, csgid, sars-cov-2, nsp16/10, transferase |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 4 |
| Total formula weight | 98349.06 |
| Authors | Minasov, G.,Shuvalova, L.,Brunzelle, J.S.,Rosas-Lemus, M.,Kiryukhina, O.,Satchell, K.J.F.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2022-04-05, release date: 2022-04-13, Last modification date: 2026-02-11) |
| Primary citation | Rosas-Lemus, M.,Athe, S.,Minasov, G.,Pattie, J.A.,Brunzelle, J.S.,Chau, I.,Li, F.,Vedadi, M.,Ma, H.,Ramanathan, A.,Becker, M.E.,Hope, T.J.,Abdelkarim, H.,Grudzien, P.,Gaponenko, V.,Montgomery, J.E.,Moellering, R.E.,Rawal, V.H.,Satchell, K.J.F. S -adenosylhomocysteine analogs selectively suppress pan-coronavirus replication by inhibition of nsp14 methyltransferase. Acs Med.Chem.Lett., 2025 Cited by PubMed Abstract: To address the ongoing threat of SARS-CoV-2 and potential emergence of novel coronaviruses, we employed a comprehensive strategy to identify and synthesize inhibitors of coronavirus methyltransferases with chemical analogs of -adenosylhomocysteine. Two analogs, designated and , inhibit both mouse hepatitis virus and SARS-CoV-2 replication. Compound was most potent with half-maximal inhibition of biochemical activity at 0.2 μM and antiviral activity at ~20 μM. This compound also has low cytotoxicity and preferentially inhibits nsp14 over nsp16 and human methyltransferases. Furthermore, molecular docking based on a newly determined crystal structure of the apo nsp16-nsp10 complex predicts occupies both the -adenosylmethione and Gppp binding pockets of nsp14 and nsp16. Selectivity of for nsp14 is likely due to enhanced structural stability of the nsp14 binding pocket relative to nsp16. These findings highlight SAH analogs as scaffolds for pan-coronavirus therapeutics and underscore the value of structure-guided design in antiviral drug discovery. PubMed: 41568342DOI: 10.1021/acsmedchemlett.5c00510 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
Download full validation report
