強力な治療抗体によるSARS-CoV-2およびSARS-CoVの中和のための構造的基礎
Zhe Lv1,2, Yong-Qiang Deng3, Qing Ye3
1CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Science (New York, N.Y.)
|July 25, 2020
まとめ
新しいヒト化モノクローン抗体H014は,スパイクタンパク質を標的として,SARS-CoV-2を効果的に中和する. この抗体はウイルス負荷を減らし,COVID-19マウスモデルにおける肺損傷を予防し,治療の可能性を示した.
科学分野:
- 免疫学とウイルス学
- 構造生物学
- 治療開発
背景:
- SARS-CoV-2によって引き起こされるCOVID-19のパンデミックは,世界的な健康上の大きな課題となっています.
- 現在,COVID-19の治療に特化した承認されたワクチンや治療薬はありません.
研究 の 目的:
- SARS-CoV-2に対する強力な中和活性を持つ新しいヒト化されたモノクローナル抗体を特定し,特徴づけること.
- 抗体の効能の仕組みと構造的根拠を調査する.
- 関連する臨床前モデルの抗体の治療可能性を評価する.
主な方法:
- SARS-CoV-2およびSARS-CoVの擬似ウイルスと本物のSARS-CoV-2を用いた中和検査.
- ヒトのアンジオテンシン変換酵素2 (ACE2) のマウスモデルでのin vivo試験
- 構造的特徴化のための冷凍電子顕微鏡 (Cryo-EM).
- 作用のメカニズムを明らかにするために生化学的,細胞的,およびウイルス学的な分析を行う.
主要な成果:
- ヒト化モノクローナル抗体H014は,ナノモラー濃度でSARS-CoV-2とSARS-CoVの効率的な中和を証明した.
- H014は,SARS-CoV-2のスパイク (S) タンパク質の受容体結合領域 (RBD) を標的とする.
- H014の投与は,感染した肺のウイルス位を低下させ,ACE2マウスモデルにおける肺病変を予防した.
- Cryo-EMは,H014が,開いた形状のRBD上の,以前に特徴づけられていない形状のエピトープに結合することを明らかにした.
- H014は,宿主細胞へのSARS-CoV-2の結合を抑制することが示されました.
結論:
- H014はSARS-CoV-2に対する強力な中和抗体であり,有望な治療候補である.
- 抗体のメカニズムは,特定の形状のエピトープをターゲットにすることで,ウイルスの結合をブロックすることを含む.
- 抗体ベースの介入は,COVID-19の治療における重要な戦略です.
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