ジャーナル: Cell / 年: 2021 タイトル: The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies. 著者: Richard Copin / Alina Baum / Elzbieta Wloga / Kristen E Pascal / Stephanie Giordano / Benjamin O Fulton / Anbo Zhou / Nicole Negron / Kathryn Lanza / Newton Chan / Angel Coppola / Joyce Chiu ...著者: Richard Copin / Alina Baum / Elzbieta Wloga / Kristen E Pascal / Stephanie Giordano / Benjamin O Fulton / Anbo Zhou / Nicole Negron / Kathryn Lanza / Newton Chan / Angel Coppola / Joyce Chiu / Min Ni / Yi Wei / Gurinder S Atwal / Annabel Romero Hernandez / Kei Saotome / Yi Zhou / Matthew C Franklin / Andrea T Hooper / Shane McCarthy / Sara Hamon / Jennifer D Hamilton / Hilary M Staples / Kendra Alfson / Ricardo Carrion / Shazia Ali / Thomas Norton / Selin Somersan-Karakaya / Sumathi Sivapalasingam / Gary A Herman / David M Weinreich / Leah Lipsich / Neil Stahl / Andrew J Murphy / George D Yancopoulos / Christos A Kyratsous / 要旨: Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. Because rapidly emerging virus mutants are becoming the next major concern in the fight ...Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. Because rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment-induced emergent resistance. To this end, we investigated the sequence diversity of the spike protein and monitored emergence of virus variants in SARS-COV-2 isolates found in COVID-19 patients treated with the two-antibody combination REGEN-COV, as well as in preclinical in vitro studies using single, dual, or triple antibody combinations, and in hamster in vivo studies using REGEN-COV or single monoclonal antibody treatments. Our study demonstrates that the combination of non-competing antibodies in REGEN-COV provides protection against all current SARS-CoV-2 variants of concern/interest and also protects against emergence of new variants and their potential seeding into the population in a clinical setting.
ダウンロード / ファイル: emd_23662.map.gz / 形式: CCP4 / 大きさ: 103 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
ボクセルのサイズ
X=Y=Z: 0.85 Å
密度
表面レベル
登録者による: 0.16 / ムービー #1: 0.16
最小 - 最大
-0.75712943 - 1.3197812
平均 (標準偏差)
0.00026167586 (±0.034575917)
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
300
300
300
Spacing
300
300
300
セル
A=B=C: 255.0 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
0.85
0.85
0.85
M x/y/z
300
300
300
origin x/y/z
0.000
0.000
0.000
length x/y/z
255.000
255.000
255.000
α/β/γ
90.000
90.000
90.000
start NX/NY/NZ
133
131
0
NX/NY/NZ
223
226
424
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
300
300
300
D min/max/mean
-0.757
1.320
0.000
-
添付データ
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試料の構成要素
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全体 : Complex of SARS-CoV-2 receptor binding domain with the Fab fragme...
全体
名称: Complex of SARS-CoV-2 receptor binding domain with the Fab fragments of neutralizing antibodies REGN10985 and REGN10989
要素
複合体: Complex of SARS-CoV-2 receptor binding domain with the Fab fragments of neutralizing antibodies REGN10985 and REGN10989
タンパク質・ペプチド: REGN10989 antibody Fab fragment light chain
タンパク質・ペプチド: REGN10989 antibody Fab fragment heavy chain
タンパク質・ペプチド: Spike protein S1
タンパク質・ペプチド: REGN10985 antibody Fab fragment light chain
タンパク質・ペプチド: REGN10985 antibody Fab fragment heavy chain
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超分子 #1: Complex of SARS-CoV-2 receptor binding domain with the Fab fragme...
超分子
名称: Complex of SARS-CoV-2 receptor binding domain with the Fab fragments of neutralizing antibodies REGN10985 and REGN10989 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all
由来(天然)
生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス)
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分子 #1: REGN10989 antibody Fab fragment light chain
分子
名称: REGN10989 antibody Fab fragment light chain / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO