7VLI

Crystal structure of Zika NS2B-NS3 protease with compound MI2220

7VLI の概要

• エントリーDOI: 10.2210/pdb7vli/pdb
• 分子名称: Serine protease subunit NS2B, NS3 protease, 1-[(3~{S},6~{S},19~{R})-3,6-bis(4-azanylbutyl)-2,5,8,12,15,18-hexakis(oxidanylidene)-1,4,7,11,14,17-hexazacyclotricos-19-yl]guanidine, ... (5 entities in total)
• 機能のキーワード: ns3 protease, viral protein
• 由来する生物種: Zika virus (ZIKV); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25610.78

構造登録者

Quek, J.P. (登録日: 2021-10-02, 公開日: 2022-08-10, 最終更新日: 2024-10-30)

主引用文献

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

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: 35475620
DOI: 10.1021/acs.jmedchem.1c01860

実験手法

X-RAY DIFFRACTION (2.385 Å)