9RQKSummary for 9RQK
| Entry DOI | 10.2210/pdb9rqk/pdb |
| Descriptor | 2C protein, (3~{S})-3-(4-iodanylphenoxy)-~{N}-methyl-3-phenyl-propan-1-amine, ZINC ION, ... (4 entities in total) |
| Functional Keywords | 2c, enterovirus, helicase, atpase, complex, antiviral, fluoxetine analogue, coxsackievirus, viral protein, drug design |
| Biological source | Coxsackievirus B3 |
| Total number of polymer chains | 1 |
| Total formula weight | 24195.99 |
| Authors | |
| Primary citation | Khemiri, S.,Faucher, M.O.,Bourg, S.,Attoumani-Madi, S.,Yaacoub, C.,Touret, F.,Farag, M.,Vitorino, M.F.,Bonnet, P.,Vanelle, P.,Aci-Seche, S.,Coutard, B.,Barral, K. New fluoxetine analogues as anti-enterovirus agents targeting 2C protein. Eur.J.Med.Chem., 306:118621-118621, 2026 Cited by PubMed Abstract: There are currently no antiviral drugs available to treat or prevent life-threatening human non-poliovirus enterovirus infections, such as those caused by CV-B3, EV-A71 or EV-D68. Our aim is to develop novel inhibitors that target the non-structural ATPase/Helicase 2C protein, which is involved in the RNA replication process that is essential for enterovirus replication, among other functions. In this study, we describe the optimization of (S)-fluoxetine, a promising hit identified through drug repurposing that binds to an allosteric site on the CV-B3 2C ATPase domain. Our optimization process was guided by rational design, X-ray crystallographic structures, computational docking, and validation by enzyme and cell-based assays, leading to several new inhibitors, among which compound 53 (CV-B3 EC = 0.5 μM and EV-D68 EC = 0.4 μM), a novel anti-enterovirus with higher selectivity indexes than (S)-fluoxetine. PubMed: 41621223DOI: 10.1016/j.ejmech.2026.118621 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.722 Å) |
Structure validation
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