EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structure-guided engineering of a mutation-tolerant inhibitor peptide against variable SARS-CoV-2 spikes.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 122, Issue 4, Page e2413465122, Year 2025
掲載日	2025年1月28日
著者	Shun Nakamura / Yukihiro Tanimura / Risa Nomura / Hiroshi Suzuki / Kouki Nishikawa / Akiko Kamegawa / Nobutaka Numoto / Atsushi Tanaka / Shigeru Kawabata / Shoichi Sakaguchi / Akino Emi / Youichi Suzuki / Yoshinori Fujiyoshi /
PubMed 要旨	Pathogen mutations present an inevitable and challenging problem for therapeutics and the development of mutation-tolerant anti-infective drugs to strengthen global health and combat evolving ...Pathogen mutations present an inevitable and challenging problem for therapeutics and the development of mutation-tolerant anti-infective drugs to strengthen global health and combat evolving pathogens is urgently needed. While spike proteins on viral surfaces are attractive targets for preventing viral entry, they mutate frequently, making it difficult to develop effective therapeutics. Here, we used a structure-guided strategy to engineer an inhibitor peptide against the SARS-CoV-2 spike, called CeSPIACE, with mutation-tolerant and potent binding ability against all variants to enhance affinity for the invariant architecture of the receptor-binding domain (RBD). High-resolution structures of the peptide complexed with mutant RBDs revealed a mechanism of mutation-tolerant inhibition. CeSPIACE bound major mutant RBDs with picomolar affinity and inhibited infection by SARS-CoV-2 variants in VeroE6/TMPRSS2 cells (IC 4 pM to 13 nM) and demonstrated potent in vivo efficacy by inhalation administration in hamsters. Mutagenesis analyses to address mutation risks confirmed tolerance against existing and/or potential future mutations of the RBD. Our strategy of engineering mutation-tolerant inhibitors may be applicable to other infectious diseases.
リンク	Proc Natl Acad Sci U S A / PubMed:39854234 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	1.7 - 8.0 Å
構造データ	39184 8ydx EMDB-39184, PDB-8ydx: Cryo-EM structure of SARS-CoV-2 spike ectodomain (HexaPro, Omicron BA.2 variant) in complex with CeSPIACE 手法: EM (単粒子) / 解像度: 4.9 Å 39185 8ydy EMDB-39185, PDB-8ydy: Cryo-EM structure of SARS-CoV-2 spike ectodomain (HexaPro, Omicron BA.5 variant) in complex with CeSPIACE, class 1 手法: EM (単粒子) / 解像度: 8.0 Å 39186 8ydz EMDB-39186, PDB-8ydz: Cryo-EM structure of SARS-CoV-2 spike ectodomain (HexaPro, Omicron BA.5 variant) in complex with CeSPIACE, class 2 手法: EM (単粒子) / 解像度: 5.2 Å PDB-8ydp: Crystal structure of the receptor binding domain of SARS-CoV-2 spike protein in complex with Ce9 手法: X-RAY DIFFRACTION / 解像度: 2.3 Å PDB-8ydq: Crystal structure of the receptor binding domain of SARS-CoV-2 Omicron BA.2 variant spike protein in complex with Ce149 手法: X-RAY DIFFRACTION / 解像度: 1.9 Å PDB-8ydr: Crystal structure of the receptor binding domain of SARS-CoV-2 Alpha variant spike protein in complex with Ce59 手法: X-RAY DIFFRACTION / 解像度: 2.3 Å PDB-8yds: Crystal structure of the receptor binding domain of SARS-CoV-2 Delta variant spike protein in complex with Ce59 手法: X-RAY DIFFRACTION / 解像度: 1.9 Å PDB-8ydt: Crystal structure of the receptor binding domain of SARS-CoV-2 Alpha variant spike protein in complex with Ce41 手法: X-RAY DIFFRACTION / 解像度: 2.5 Å PDB-8ydu: Crystal structure of the receptor binding domain of SARS-CoV-2 Omicron BA.2 variant spike protein in complex with CeSPIACE 手法: X-RAY DIFFRACTION / 解像度: 1.7 Å PDB-8ydv: Crystal structure of the receptor binding domain of SARS-CoV-2 Omicron BA.5 variant spike protein in complex with CeSPIACE 手法: X-RAY DIFFRACTION / 解像度: 2.2 Å PDB-8ydw: Crystal structure of the receptor binding domain of SARS-CoV-2 Omicron XBB.1.5 variant spike protein in complex with CeSPIACE 手法: X-RAY DIFFRACTION / 解像度: 2 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-GOL: GLYCEROL / グリセロ-ル ChemComp-HOH: WATER ChemComp-NA: Unknown entry / ナトリウムカチオン
由来	severe acute respiratory syndrome coronavirus 2 (ウイルス) synthetic construct (人工物)
キーワード	VIRAL PROTEIN/INHIBITOR / RBD / VIRAL PROTEIN-INHIBITOR COMPLEX / Spike protein