Japan Agency for Medical Research and Development (AMED)
20fk0108295h0001
日本
Japan Agency for Medical Research and Development (AMED)
2833
日本
引用
ジャーナル: PLoS Pathog / 年: 2021 タイトル: Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model. 著者: Kei Haga / Reiko Takai-Todaka / Yuta Matsumura / Chihong Song / Tomomi Takano / Takuto Tojo / Atsushi Nagami / Yuki Ishida / Hidekazu Masaki / Masayuki Tsuchiya / Toshiki Ebisudani / Shinya ...著者: Kei Haga / Reiko Takai-Todaka / Yuta Matsumura / Chihong Song / Tomomi Takano / Takuto Tojo / Atsushi Nagami / Yuki Ishida / Hidekazu Masaki / Masayuki Tsuchiya / Toshiki Ebisudani / Shinya Sugimoto / Toshiro Sato / Hiroyuki Yasuda / Koichi Fukunaga / Akihito Sawada / Naoto Nemoto / Kazuyoshi Murata / Takuya Morimoto / Kazuhiko Katayama / 要旨: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying ...The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed, particularly for treating life-threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited SARS-CoV-2 titers in infected lungs of Syrian hamsters without causing weight loss and cytokine induction. In vitro studies demonstrated that K-874A neutralized SARS-CoV-2 in both VeroE6/TMPRSS2 and human lung-derived alveolar organoid cells. Unlike other drug candidates, K-874A blocks viral membrane fusion rather than viral attachment. Cryo-electron microscopy revealed K-874A bound between the receptor binding domain and N-terminal domain of the virus S protein. Further, infected cells treated with K-874A produced fewer virus progeny that were less infective. We propose that direct administration of K-874A to the lung could be a new treatment for preventing the reinfection of amplified virus in COVID-19 patients.
ダウンロード / ファイル: emd_31575.map.gz / 形式: CCP4 / 大きさ: 2.8 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
Major cryo-EM structure of S protein trimer of SARS-CoV2 with K-874A VHHs, focused refinement of K-874A, RBD and NTD
ボクセルのサイズ
X=Y=Z: 1.11 Å
密度
表面レベル
登録者による: 0.033 / ムービー #1: 0.033
最小 - 最大
-0.14712207 - 0.18792038
平均 (標準偏差)
0.00021041401 (±0.012239078)
対称性
空間群: 1
詳細
EMDB XML:
マップ形状
Axis order
X
Y
Z
Origin
0
0
0
サイズ
90
90
90
Spacing
90
90
90
セル
A=B=C: 99.9 Å α=β=γ: 90.0 °
CCP4マップ ヘッダ情報:
mode
Image stored as Reals
Å/pix. X/Y/Z
1.11
1.11
1.11
M x/y/z
90
90
90
origin x/y/z
0.000
0.000
0.000
length x/y/z
99.900
99.900
99.900
α/β/γ
90.000
90.000
90.000
start NX/NY/NZ
-220
-220
-220
NX/NY/NZ
440
440
440
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
90
90
90
D min/max/mean
-0.147
0.188
0.000
-
添付データ
-
試料の構成要素
-
全体 : Major cryo-EM structure of S protein trimer of SARS-CoV2 with K-8...
全体
名称: Major cryo-EM structure of S protein trimer of SARS-CoV2 with K-874A VHHs, focused refinement of K-874A, RBD and NTD
要素
複合体: Major cryo-EM structure of S protein trimer of SARS-CoV2 with K-874A VHHs, focused refinement of K-874A, RBD and NTD
-
超分子 #1: Major cryo-EM structure of S protein trimer of SARS-CoV2 with K-8...
超分子
名称: Major cryo-EM structure of S protein trimer of SARS-CoV2 with K-874A VHHs, focused refinement of K-874A, RBD and NTD タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2
由来(天然)
生物種: Severe acute respiratory syndrome-related coronavirus (ウイルス)
組換発現
生物種: Homo sapiens (ヒト) / 組換細胞: RAW264.7 / 組換プラスミド: cDNA