7VLG
Crystal structure of Zika NS2B-NS3 protease with compound MI2201
Summary for 7VLG
| Entry DOI | 10.2210/pdb7vlg/pdb |
| Descriptor | Serine protease subunit NS2B, NS3 protease, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | ns3 protease, viral protein |
| Biological source | Zika virus (ZIKV) More |
| Total number of polymer chains | 2 |
| Total formula weight | 25671.90 |
| Authors | Quek, J.P. (deposition date: 2021-10-02, release date: 2022-08-10, Last modification date: 2023-11-29) |
| Primary citation | Huber, S.,Braun, N.J.,Schmacke, L.C.,Quek, J.P.,Murra, R.,Bender, D.,Hildt, E.,Luo, D.,Heine, A.,Steinmetzer, T. Structure-Based Optimization and Characterization of Macrocyclic Zika Virus NS2B-NS3 Protease Inhibitors. J.Med.Chem., 65:6555-6572, 2022 Cited by PubMed Abstract: Zika virus (ZIKV) is a human pathogenic arbovirus. So far, neither a specific treatment nor a vaccination against ZIKV infections has been approved. Starting from our previously described lead structure, a series of 29 new macrocyclic inhibitors of the Zika virus protease containing different linker motifs have been synthesized. By selecting hydrophobic d-amino acids as part of the linker, numerous inhibitors with values < 5 nM were obtained. For 12 inhibitors, crystal structures in complex with the ZIKV protease up to 1.30 Å resolution were determined, which contribute to the understanding of the observed structure-activity relationship (SAR). In immunofluorescence assays, an antiviral effect was observed for compound containing a d-homocyclohexylalanine residue in its linker segment. Due to its excellent selectivity profile and low cytotoxicity, this inhibitor scaffold could be a suitable starting point for the development of peptidic drugs against the Zika virus and related flaviviruses. PubMed: 35475620DOI: 10.1021/acs.jmedchem.1c01860 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.771 Å) |
Structure validation
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