+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8el2 | ||||||
---|---|---|---|---|---|---|---|
タイトル | SARS-CoV-2 RBD bound to neutralizing antibody Fab ICO-hu23 | ||||||
要素 |
| ||||||
キーワード | ANTIVIRAL PROTEIN/IMMUNE SYSTEM / Fab / SARS-CoV-2 / receptor-binding domain / neutralizing antibody / ANTIVIRAL PROTEIN / ANTIVIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
機能・相同性 | 機能・相同性情報 Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Severe acute respiratory syndrome coronavirus 2 (ウイルス) | ||||||
手法 | X線回折 / シンクロトロン / 分子置換 / 解像度: 2.89 Å | ||||||
データ登録者 | Besaw, J.E. / Kuo, A. / Morizumi, T. / Ernst, O.P. | ||||||
資金援助 | カナダ, 1件
| ||||||
引用 | ジャーナル: PLoS Pathog / 年: 2023 タイトル: Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates. 著者: Paule Hermet / Benoît Delache / Cecile Herate / Esther Wolf / Gaily Kivi / Erkki Juronen / Karl Mumm / Eva Žusinaite / Denis Kainov / Eve Sankovski / Kai Virumäe / Anu Planken / Andres ...著者: Paule Hermet / Benoît Delache / Cecile Herate / Esther Wolf / Gaily Kivi / Erkki Juronen / Karl Mumm / Eva Žusinaite / Denis Kainov / Eve Sankovski / Kai Virumäe / Anu Planken / Andres Merits / Jessica E Besaw / Ai Woon Yee / Takefumi Morizumi / Kyumhyuk Kim / Anling Kuo / Asma Berriche / Nathalie Dereuddre-Bosquet / Quentin Sconosciuti / Thibaut Naninck / Francis Relouzat / Mariangela Cavarelli / Mart Ustav / Derek Wilson / Oliver P Ernst / Andres Männik / Roger LeGrand / Mart Ustav / 要旨: The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of ...The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants. Furthermore, cumbersome systemic administration limits easy and broad access to such drugs. As well, concentrations of systemically administered antibodies in the mucosal epithelium, a primary site of initial infection, are dependent on neonatal Fc receptor mediated transport and require high drug concentrations. To reduce the viral load more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2 neutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-neutralizing properties. Administration of this antibody via a vibrating mesh nebulization device retained antibody integrity and resulted in effective distribution of the antibody in the upper and lower respiratory tract of non-human primates (NHP). In comparison with intravenous administration, significantly higher antibody concentrations can be obtained in the lung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This approach may reduce the barriers of access and uptake of antibody therapeutics in real-world clinical settings and provide a more effective blueprint for targeting existing and potentially emerging respiratory tract viruses. | ||||||
履歴 |
|
-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
---|
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8el2.cif.gz | 258.7 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb8el2.ent.gz | 201.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8el2.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 8el2_validation.pdf.gz | 511.3 KB | 表示 | wwPDB検証レポート |
---|---|---|---|---|
文書・詳細版 | 8el2_full_validation.pdf.gz | 538.6 KB | 表示 | |
XML形式データ | 8el2_validation.xml.gz | 45.9 KB | 表示 | |
CIF形式データ | 8el2_validation.cif.gz | 62.3 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/el/8el2 ftp://data.pdbj.org/pub/pdb/validation_reports/el/8el2 | HTTPS FTP |
-関連構造データ
関連構造データ | 8eljC 7behS S: 精密化の開始モデル C: 同じ文献を引用 (文献) |
---|---|
類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
2 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
単位格子 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Components on special symmetry positions |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
非結晶学的対称性 (NCS) | NCSドメイン:
NCSドメイン領域:
|